N-arylsulfonyl-3-aminoalkoxyindoles

ABSTRACT

N-arylsulfonyl-3-aminoalkoxyindoles indole compounds, radioisotopes, stereoisomers, geometric forms, N-oxides, polymorphs and pharmaceutically acceptable salts.

This application is a divisional of U.S. application Ser. No. 10/536,592filed on May 26, 2005, which is a Sect. 371 National Stage of PCTInternational Application No. PCT/IN2003/000370, filed on Nov. 25, 2003,claiming priority of Indian Patent Application No. 883/MAS/2002 filed onNov. 28, 2002, the contents of both applications which are herebyincorporated by reference.

FIELD OF INVENTION

The present invention includes compounds described by general formula(I), its stereoisomers, its radioisotopes, its geometric forms, itsN-oxides, its polymorphs, its pharmaceutically acceptable salts, itspharmaceutically acceptable solvates, its useful bio-active metabolitesand any suitable combination of the above.

Further the present invention also includes the processes for preparingsuch compounds of the general formula (I), its stereoisomers, itsradioisotopes, its geometric forms, its N-oxides, its polymorphs, itspharmaceutically acceptable salts, its pharmaceutically acceptablesolvates, its useful bioactive metabolites and also includes anysuitable combination of the above.

The invention also describes various methods of administering thesecompounds of general formula (I), i.e. pharmaceutically acceptabledosage forms compositions and the use of such compounds and compositionsin either therapy or diagnosis.

The compounds of the general formula (I) of this invention are 5-HT(Serotonin) ligands e.g. agonists or antagonists. The compounds of thegeneral formula (I) of this invention, by the virtue of its chemicalcharacteristic, could either independently or simultaneously modulatethe melatonin receptor i.e. either these compounds are melatonergicligands e.g. agonists or antagonists, or they interact with both 5-HTand/or Melatonin receptors.

Thus, compounds of general formula (I) of this invention are useful fortreating diseases wherein activity of either 5-HT (Serotonin) and/orMelatonin is modulated to obtain the desired therapeutic effect.Specifically, the compounds of this invention are useful in thetreatment and/or prophylaxis of conditions such as psychosis,paraphrenia, psychotic depression, mania, schizophrenia,schizophreniform disorders, anxiety, migraine headache, depression, drugaddiction, convulsive disorders, personality disorders, hypertension,autism, post-traumatic stress syndrome, alcoholism, panic attacks,obsessive-compulsive disorders, chronobiological abnormalities,circadian rhythms, anxiolytic, osteoporosis, ischemic stroke, lower therisk of SIDS in young infants with low endogenous melatonin levels,reproduction, glaucoma and sleep disorders.

Hence, the compounds of general formula (I) of this invention could alsobe useful in treating the psychotic, affective, vegetative andpsychomotor symptoms of schizophrenia and the extrapyramidal motor sideeffects of other antipsychotic drugs; neurodegenerative disorders likeAlzheimer's disease, Parkinson's and Huntington's chorea andchemotherapy-induced vomiting; and in modulation of eating behavior andthus are useful in reducing the morbidity and mortality associated withexcess weight.

BACKGROUND OF THE INVENTION

Many diseases of the central nervous system are influenced by theadrenergic, the dopaminergic and the serotoninergic neurotransmittersystems. Serotonin has been implicated in numerous diseases andconditions, which originate from central nervous system. The listincludes diseases and conditions related to sleeping, eating, perceivingpain, controlling body temperature, controlling blood pressure,depression, anxiety, schizophrenia and other bodily states. (References:Fuller, R. W., Drugs Acting on Serotoninergic Neuronal Systems, in“Biology of Serotoninergic Transmission”, ed. by Osborne N. N., J Wiley& Sons Inc. (1982), 221-247; Boullin D. J., et. al., in “Serotonin inMental Abnormalities”, International Association for The ScientificStudy of Mental Deficiency, Wiley, Checester, 1978, pp. 1-340; BarchasJ. et. al., in “Serotonin and Behavior”, Academic Press, NY (1973)).Serotonin also plays an important role in the peripheral systems, suchas the gastrointestinal system, where it has been found to mediate avariety of contractile, secretory and electrophysiologic effects.

Due to the broad distribution of serotonin within the body, there is alot of interest and use, in the drugs that affect serotoninergicsystems. Particularly, preferred are the compounds which havereceptor-specific agonism and/or antagonism for the treatment of a widerange of disorders, including anxiety, depression, hypertension,migraine, obesity, compulsive disorders, schizophrenia, autism, certainother neurodegenerative disorders like Alzheimer, Parkinson,Huntington's chorea and chemotherapy-induced vomiting (References:Gershon M. D. et. al., 5-Hydroxytryptamine and enteric neurons. In: ThePeripheral Actions of 5-Hydroxytryptamine, edited by J. R. Fozard. NewYork: Oxford, 1989, p. 247-273; Saxena P. R., et. al., Journal ofCardiovascular Pharmacology (1993), supplement 15, p. 17-34).

The major classes of serotonin receptors (5-HT₁₋₇) contain fourteen toeighteen separate receptors that have been formally classified(References: Glennon et al, Neuroscience and Behavioral Reviews (1990),14, 35; and Hoyer D. et al, Pharmacol. Rev. (1994), 46, 157-203).Recently discovered information regarding sub-type identity,distribution, structure and function suggests that it is possible toidentify novel, sub-type specific agents having improved therapeuticprofiles with lesser side effects. The 5-HT₆ receptor was identified in1993 (References: Monsma et al, Mol. Pharmacol. (1993), 43, 320-327; andRuat M. et al, Biochem. Biophys. Res. Com. (1993), 193, 269-276).Several antidepressants and atypical antipsychotics bind to the 5-HT₆receptor with high affinity and this binding may be a factor in theirprofile of activities (References: Roth et al, J. Pharm. Exp. Therapeut.(1994), 268, 1403-1410; Sleight et al, Exp. Opin. Ther. Patents (1998),8, 1217-1224; Bourson et al, Brit. J. Pharmacol. (1998), 125, 1562-1566;Boess et al, Mol. Pharmacol., 1998, 54, 577-583; Sleight et al, Brit. J.Pharmacol. (1998), 124, 556-562). In addition, 5-HT₆ receptor has beenlinked to generalized stress and anxiety states (Reference: Yoshioka etal, Life Sciences (1998), 17/18, 1473-1477). Together these studies andobservations suggest that the compound, which antagonizes 5-HT₆receptors, will be useful in treating various disorders of the centralnervous system.

There is very strong evidence that Melatonin is important for theregulation of a variety of neural and endocrine functions, especiallythose that exhibit circadian and circannual rhythmicity. Great interesttherefore lies in the possibility of making available to the clinicianmelatonin analogues that are metabolically more stable and have anagonist or antagonist character and of which the therapeutic effect maybe expected to be superior to that of the hormone itself. PCT patentapplication WO 00/72815 and U.S. Pat. No. 6,465,660B1 gives extensiveliterature on studies with Melatonin and potential therapeuticapplication of various ligands reported till date.

Those various effects are exerted via the intermediary of specificMelatonin receptors. Molecular biology studies have demonstrated theexistence of a number of receptor sub-types that are capable of bindingthat hormone (Trends Pharmacol. Sci., 1995, 16, p. 50; WO 97 04094).Melatonin acts on the CNS to affect neural mechanisms through receptorslocated in the brain. Additionally, a number of studies indicate theexistence of direct effects of Melatonin in peripheral organs viaperipheral melatonin receptors. Melatonin receptors are present in theheart, lungs, prostate gland, gonads, white blood cells, retina,pituitary, thyroid, kidney, gut and blood vessels (Withyachumnamkul etal., Life Sci, 12 65, 1986). Three Melatonin receptor subtypes have beenidentified so far MT-1, MT-2 and MeI 1 c (Barreft et al., Biol. SignalsRecept., 1999, 8: 6-14).

There is evidence suggesting both Melatonin agonists and antagonistswould be of potential therapeutic use for a variety of maladies andconditions. PCT application WO 00/72815 and U.S. Pat. No. 6,465,660B1discuss in depth applications and use of such compounds and details ofwhich are incorporated herein by reference. Also U.S. Pat. No. 6,465,660and U.S. patent application publication number U.S. 2003/0105087 discusssome tricyclic indole and tricyclic azaindole derivatives having veryvaluable pharmacological characteristics in respect of melatoninergicreceptors.

U.S. Pat. No. 4,839,377 and U.S. Pat. No. 4,855,314 refers to5-substituted 3-aminoalkyl indoles. The compounds are said to be usefulfor the treatment of migraine.

British Patent 2,035,310 refers to 3-aminoalkyl-1H-indole-5-thioamidesand carboxamides. The compounds are said to be useful in treatinghypertension, Raymond's disease and migraine.

European Patent Publication 303,506 refers to3-polyhydropyridyl-5-substituted-1H-indoles. The compounds are said tohave 5-HT₁ receptor agonists and vasoconstrictor activity and to beuseful in treating migraine. European Patent Publication 354,777 refersto N-piperidinylindolylethyl-alkane sulfonamide derivatives. Thecompounds are said to be 5-HT₁ receptor agonists and havevasoconstrictor activity and are useful in treating cephalic pain.

European Patent Publication 438,230, refers to indole-substitutedfive-membered heteroaromatic compounds. The compounds are said to have“5-HT₁-like” receptor agonist activity and to be useful in the treatmentof migraine and other disorders for which a selective agonist of thesereceptors is indicated.

European Patent Publication 313,397 refers to 5-heterocyclic indolederivatives. The compounds are said to have exceptional properties forthe treatment and prophylaxis of migraine, cluster headache and headacheassociated with vascular disorders. These compounds are also said tohave exceptional “5-HT₁-like” receptor agonism.

International Patent Publication WO 91/18897 refers to 5-heterocyclicindole derivatives. The compounds are said to have exceptionalproperties for the treatment and prophylaxis of migraine, clusterheadache, and headache associated with vascular disorders. Thesecompounds are also said to have exceptional “5-HT₁-like” receptoragonism.

European Patent Publication 457,701 refers to aryloxy amine derivativesas having high affinity for 5-HT_(1D) serotonin receptors. Thesecompounds are said to be useful for treating diseases related toserotonin receptor dysfunction, for example, migraine.

European Patent Publication 497,512 A2, refers to a class of imidazole,triazole and tetrazole derivatives that are selective agonists for“5-HT₁-like” receptors. These compounds are said to be useful fortreating migraine and associated disorders.

International Patent Publication WO 93/00086 describes a series oftetrahydrocarbazole derivatives, as 5-HT₁ receptor agonists, useful forthe treatment of migraine and related conditions.

International Patent Publication WO 93/23396, refers to fused imidazoleand triazole derivatives as 5-HT₁ receptor agonists, for the treatmentof migraine and other disorders.

Schoeffter P. et al. refers to methyl4-{4-[4-(1,1,3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl]-1-piperazinyl}1H-indole-3-carboxylateas a selective antagonist for the 5-HT_(1A) receptor in their paper“SDZ216-525, a selective and potent 5-HT_(1A) receptor antagonist”,European Journal of Pharmacology, 244, 251-257 (1993).

International Patent Publication WO 94/06769, refers to2-substituted-4-piperazine-benzothiophene derivatives that are serotonin5-HT_(1A) and 5-HT_(1D) receptor agents useful in the treatment ofanxiety, depression, migraine, stroke, angina and hypertension.

SUMMARY OF THE INVENTION

The present invention relates to compounds of general formula (I), itsstereoisomers, its radioisotopes, its geometric forms, its N-oxide, itspolymorphs, its pharmaceutically acceptable salts, its pharmaceuticallyacceptable solvates, its useful bio-active metabolites and any suitablecombination of the above.

The compounds of general formula (I) are as follows,

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₁ and R₁₂ may be same ordifferent, and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio,amino, nitro, cyano, formyl, amidino, guanidino, substituted orunsubstituted groups selected from linear or branched (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, (C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl,(C₃-C₇)cycloalkenyl, bicycloalkyl, bicycloalkenyl, (C₁-C₁₂)alkoxy,cyclo(C₃-C₇)alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl,heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino,alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl,aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkoxyalkylarylalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino,aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino,alkylamidino, alkylguanidino, dialkylguanidino, hydrazino,hydroxylamino, carboxylic acid and its derivatives, sulfonic acids andits derivatives, phosphoric acid and its derivatives; or the adjacentgroups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ andR₇ or R₇ and R₈ or R₈ and R₉ together with carbon atoms to which theyare attached may form a five or a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; or R₁₁ and R₁₂ together with carbon atoms to which theyare attached may form a three to a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms.

R₁₀ represents hydrogen, halogen, perhaloalkyl, substituted orunsubstituted groups selected from linear or branched (C₁-C₃)alkyl andaryl.

R₁₃ and R₁₄ represents hydrogen, alkyl, aryl, aralkyl or together withnitrogen atom form a cyclic three to seven membered ring,

optionally, R₁₁ and R₁₃ together may form a part of cyclic structurealong with the intervening nitrogen and carbon atoms; the heterocyclemay have either one, two or three double bonds; optionally it may alsocontain one to three heteroatom selected from the group of oxygen,nitrogen and sulfur, and includes ring fused with any carbocyclic orheterocyclic ring, which can be saturated or unsaturated.

“n” is an integer ranging from 1 to 8, preferably 1 to 4, wherein thecarbon chains which “n” represents may be either linear or branched.

“m” is an integer ranging from 0 to 2 preferably m is 1 or 2; along withthe proviso that whenever m=2 and each of R₅, R₆, R₇, R₈ and R₉ arehydrogens then all of R₁, R₂, R₃, R₄ and R₁₀, together are neverhydrogens.

Partial List of Such Compounds of General Formula (I) is as Follows:

-   [2-(1-(Benzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(2′-Bromobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Fluorobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Chlorobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Methylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(Benzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Methylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(Benzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Fluorobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Chlorobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Methylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(Benzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-4′-Bromo-4′-methoxybenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-6-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-6-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2-Bromobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Methylbenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(Benzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4-methoxybenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4-Methylbenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4-Chlorobenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4-Chlorobenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)    ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4-Methylbenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)    ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine-   [2-(1-(4′-Isopropylbenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4*-Isopropylbenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-7-bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(Benzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Isopropylbenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′,4′-Dimethoxybenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Bromobenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromo,4′-Methylbenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Fluorobenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Chlorobenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-5-fluoro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-fluoro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(4′-Methylbenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-Benzenesulfonyl-5-nitro-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine;-   [2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine;    or a stereoisomer, or a polymorph, or any suitable combination of    above such as a nitrogen oxide thereof; a prodrug of the compound or    the nitrogen oxide; a pharmaceutically acceptable salt of the    compound, the nitrogen oxide, or the prodrug; or a solvate or    hydrate of the compound, the nitrogen oxide, the prodrug or the    pharmaceutically acceptable salt.

The present invention also relates to the process for preparing thecompound of the general formula (I) its stereoisomers, itsradioisotopes, its geometric forms, its N-oxide, its polymorphs, itspharmaceutically acceptable salts, its pharmaceutically acceptablesolvates, its useful bioactive metabolites and any suitable combinationof above.

In the case of the compounds of general formula (I), where tautomerismmay exist, the present invention relates to all of the possibletautomeric forms and the possible mixture thereof.

The present invention also relates to the stereoisomers, which as a ruleare obtained as racemates that can be separated into the opticallyactive isomers in a manner known per se.

The present invention also relates to radio-labeled isotopes, which areidentical to those defined in the general formula (I), but for the factthat one or more atoms are replaced by an atom having an atomic mass ormass number different from the atomic mass or mass number found usuallyin nature. Examples of isotopes that can be incorporated into compoundsof the invention include isotopes of hydrogen, carbon, nitrogen, oxygen,phosphorus, fluorine, chlorine, iodine, bromine and mTecnitium,exemplified by ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ¹⁸F, ^(99m)Tc, ³¹P,S, ¹²³I and ¹²⁵I. Those compounds of general formula (I) as describedearlier containing the aforementioned isotopes and/or other isotopes ofother atoms are within the scope of this invention.

In the case of the compounds of general formula (I) containing geometricisomerism the present invention relates to all of these geometricisomers.

The term “nitrogen oxide” or “N-oxide” refers to the oxidation of atleast one of the two nitrogens in the compounds of general formula (I)(e.g., mono- or di-oxide). The nitrogen mono-oxides may exist as asingle positional isomer or a mixture of 2° positional isomers (e.g., amixture of 1-N-oxide and 4-N-oxide piperazine or a mixture of 1-N-oxideand 4-N-oxide piperazines).

Suitable pharmaceutically acceptable acid addition salts of compounds ofthe general formula (I) can be prepared of the aforementioned basecompounds of this invention are those which form non-toxic acid additionsalts, includes, salts containing pharmacologically acceptable anions,such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate,bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acidcitrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate,saccharate, benzoate, methanesulfonate, ethanesulfonate,benzenesulfonate, p-toluenesulfonate, palmoate and oxalate.Pharmaceutically acceptable salts forming part of this invention areintended to define but not limited to the above list.

Suitable pharmaceutically acceptable base addition salts of compounds ofthe general formula (I) can be prepared of the aforementioned acidcompounds of this invention are those which form non-toxic base additionsalts, includes, salts containing pharmaceutically acceptable cations,such as Lithium, sodium, potassium, calcium and magnesium, salts oforganic bases such as, lysine, arginine, guanidine, diethanolamine,choline, tromethamine and the like; ammonium or substituted ammoniumsalts.

Pharmaceutically acceptable salts forming part of this invention areintended to define but not limited to the above list.

In addition, pharmaceutically acceptable salts of the compound offormula (I) can be obtained by converting derivatives which havetertiary amino groups into the corresponding quarternary ammonium saltsin the methods known in the literature by using quarternizing agents.Possible quarternizing agents are, for example, alkyl halides such asmethyl iodide, ethyl bromide and n-propyl chloride, including arylalkylhalides such as benzyl chloride or 2-phenylethyl bromide.

In the addition to pharmaceutically acceptable salts, other salts areincluded in the invention. They may serve as intermediates in thepurification of the compounds, in the preparation of other salts, or inthe identification and characterization of the compounds orintermediates.

The pharmaceutically acceptable salts of compounds of formula (I) mayexists as solvates, such as with water, methanol, ethanol,dimethylformamide, ethyl acetate, and the like. Mixtures of suchsolvates can also be prepared. The source of such solvate can be fromthe solvent of crystallization, inherent in the solvent preparation orcrystallization, or adventitious to such solvent. Such solvates arewithin the scope of this invention.

The invention also encompasses the pharmaceutically acceptable prodrugsof the compounds of the formula (I). A prodrug is a drug which has beenchemically modified and may be biologically in-active at the site ofaction, but which may be degraded or modified by one or more enzymaticor other in-vivo processes to the parent form. This prodrug should havea different pharmacokinetic profile than the parent, enabling easierabsorption across the mucosal epithelium, better salt formation, orsolubility, and/or improved systemic stability (an increase in theplasma half-life, for example). Typically, such chemical modificationsinclude the following:

-   -   1. ester or amide derivatives which may be cleaved by esterases        or lipases;    -   2. peptides which may be recognized by specific or non-specific        proteases; or    -   3. derivatives that accumulate at a site of action through        membrane selection of a prodrug from or a modified prodrug form;        or    -   4. any combination of 1 to 3, above.

Conventional procedures for the selection and preparation of suitableprodrug derivatives are described, for example, in H. Bundgard, Designof prodrugs, (1985).

Another aspect of the present invention comprises of a pharmaceuticalcomposition, containing at least one of the compounds of the generalformula (I), their derivatives, their analogs, their derivatives, theirstereoisomers, their polymorphs, their pharmaceutically acceptablesalts, their pharmaceutically acceptable solvates thereof as an activeingredient, together with pharmaceutically employed carriers,auxiliaries and the like.

An effective amount of a compound of general formula (I) or its salt isused for producing medicaments of the present invention, along withconventional pharmaceutical auxiliaries, carriers and additives.

The present invention also relates to the pharmaceutically acceptablecompositions containing them, and the use of these compounds andcompositions in medicine.

The compounds of general formula (I) of this invention are useful in thetreatment and/or prophylaxis of a condition wherein modulation of 5-HTactivity is desired.

The compounds of general formula (I) of this invention are useful in thetreatment and/or prophylaxis of a condition wherein modulation ofmelatonin activity is desired.

The compounds of general formula (I) of this invention are useful in thetreatment and/or prophylaxis of a condition wherein modulation of 5-HTand melatonin activities gives desired effect.

The present invention provides for use of the compounds of generalformula (I) according to above, for the manufacture of the medicamentsfor the potential use in the treatment and/or prophylaxis of certain CNSdisorders such as, anxiety, depression, convulsive disorders,obsessive-compulsive disorders, migraine headache, cognitive memorydisorders e.g. Alzheimer's disease and age-related cognitive decline,ADHD (Attention Deficient Disorder/Hyperactivity Syndrome), personalitydisorders, psychosis, paraphrenia, psychotic depression, mania,schizophrenia, schizophreniform disorders, withdrawal from drug abusesuch as cocaine, ethanol, nicotine and benzodiazepines, panic attacks,chronobiological abnormalities, circadian rhythms, anxiolytic,osteoporosis, ischemic stroke, lower the risk of SIDS in young infantswith low endogenous melatonin levels, reproduction, glaucoma, sleepdisorders (including disturbances of Circadian rhythm) and alsodisorders associated with spinal trauma and/or head injury such ashydrocephalus. Compounds of the invention are further expected to be ofuse in the treatment of mild cognitive impairment and otherneurodegenerative disorders like Alzheimer's disease, Parkinsonism andHuntington's chorea.

The compounds of the invention are also expected to be of use in thetreatment of certain GI (Gastrointestinal) disorders such as IBS(Irritable bowel syndrome) or chemotherapy induced emesis.

The compounds of the invention are also expected to be of use in themodulation of eating behavior and these compounds can also be used toreduce morbidity and mortality associated with the excess weight.

The present invention provides a method for the treatment of a human ora animal subject suffering from certain CNS disorders such as, anxiety,depression, convulsive disorders, obsessive-compulsive disorders,migraine headache, cognitive memory disorders e.g. Alzheimer's diseaseand age-related cognitive decline, ADHD (Attention DeficientHyperactivity Disorder), personality disorders, psychosis, paraphrenia,psychotic depression, mania, schizophrenia, schizophreniform disorders,withdrawal from drug abuse such as cocaine, ethanol, nicotine andbenzodiazepines, panic attacks, chronobiological abnormalities,circadian rhythms, anxiolytic, osteoporosis, ischemic stroke, lower therisk of SIDS in young infants with low endogenous melatonin levels,reproduction, glaucoma, sleep disorders (including disturbances ofCircadian rhythm) and also disorders associated with spinal traumaand/or head injury such as hydrocephalus. Compounds of the invention arefurther expected to be of use in the treatment of mild cognitiveimpairment and other neurodegenerative disorders like Alzheimer'sdisease, Parkinsonism and Huntington's chorea.

The present invention also provides a method for modulating 5-HT and/ormelatonin receptor function desired in certain cases.

Compounds of the present invention may be administered in combinationwith other pharmaceutical agents, such as apo-B/MTP inhibitors, MCR-4agonists, CCK-A agonists, monoamine reuptake inhibitors, sympathomimeticagents, adrenergic receptor agonists, dopamine agonists,melanocyte-stimulating hormone receptor analogs, cannabinoid 1 receptorantagonists, melanin concentrating hormone antagonists, leptins, leptinanalogs, leptin receptor agonists, galanin antagonists, lipaseinhibitors, bombesin agonists, neuropeptide-Y antagonists, thyromimeticagents, dehydroepiandrosterone or analogs thereof, glucocorticoidreceptor agonists or antagonists, orexin receptor antagonists, urocortinbinding protein antagonists, glucagon-like peptide-1 receptor agonists,ciliary neurotrophic factors, AGRPs (human agouti-related proteins),ghrelin receptor antagonists, histamine 3 receptor antagonists orreverse agonists, neuromedin U receptor agonists, and the like, in atherapeutically effective amount via a suitable pharmaceuticalcomposition, to achieve the desired effect in mammals as well as humans.

The phrase “pharmaceutically acceptable” indicates that the substance orcomposition must be compatible chemically and/or toxicologically, withthe other ingredients comprising a formulation, and/or the mammal beingtreated therewith.

The terms “treating”, “treat”, or “treatment” embrace all the meaningssuch as preventative, prophylactic and palliative.

The term “compounds of the present invention” (unless specificallyidentified otherwise) refer to compounds of Formulae (I), nitrogenoxides thereof, prodrugs of the compounds or nitrogen oxides,pharmaceutically acceptable salts of the compounds, nitrogen oxides,and/or prodrugs, and hydrates or solvates of the compounds, nitrogenoxides, salts, is and/or prodrugs, as well as, all stereoisomers(including diastereoisomers and enantiomers), tautomers and isotopicallylabeled compounds.

The present invention also relates to the novel intermediates,represented by genera) formulae (II), (VI), (VII) and (IX) theirstereoisomers, their radioisotopes, their geometric forms, theirN-oxide, their salts, their solvates and any suitable combination ofabove, involved in preparing the compounds of general formula (I) andthe process of preparation of such intermediates.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compounds of general formula (I), theirstereoisomers, their radioisotopes, their geometric forms, theirN-oxides, their polymorphs, their pharmaceutically acceptable salts,their pharmaceutically acceptable solvates, their useful bioactivemetabolites and any suitable combination of above.

The present invention relates to compounds of general formula (I),described as follows,

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₁ and R₁₂ may be same ordifferent, and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio,amino, nitro, cyano, formyl, amidino, guanidino, substituted orunsubstituted groups selected from linear or branched (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, (C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl, (CVC₇)cycloalkenyl, bicycloalkyl, bicycloalkenyl, (C₁-C₁₂)alkoxy,cyclo(C₃-C₇)alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl,heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino,alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl,aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkoxyalkylarylalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino,aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino,alkylamidino, alkylguanidino, dialkylguanidino, hydrazino,hydroxylamino, carboxylic acid and its derivatives, sulfonic acids andits derivatives, phosphoric acid and its derivatives; or the adjacentgroups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ andR₇ or R₇ and R₈ or R₈ and R₈ together with carbon atoms to which theyare attached may form a five or a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; or R₁₁ and R₁₂ together with carbon atoms to which theyare attached may form a three to a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms.R₁₀ represents hydrogen, halogen, perhaloalkyl, substituted orunsubstituted groups selected from linear or branched (C₁-C₃)alkyl andaryl.

R₁₃ and R₁₄ represents hydrogen, alkyl, aryl, aralkyl or together withnitrogen atom form a cyclic three to seven membered ring, optionally,R₁₁ and R₁₃ together may form a part of cyclic structure along with theintervening nitrogen and carbon atoms; the heterocycle may have eitherone, two or three double bonds; optionally it may also contain one tothree heteroatom selected from the group of oxygen, nitrogen and sulfur,and includes ring-fused with any carbocyclic or heterocyclic ring, whichcan be saturated or unsaturated.

“n” is an integer ranging from 1 to 8, preferably 1 to 4, wherein thecarbon chains which “n” represents may be either linear or branched.

“m” is an integer ranging from 0 to 2 preferably m is 1 or 2; along withthe proviso that whenever m=2 and each of R₅, R₆, R₇, R₈ and R₉ arehydrogens then all of R₁, R₂, R₃, R₄ and R₁₀) together are neverhydrogens.

Suitable groups represented by R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀,R₁₁ and R₁₂ wherever applicable may be selected from halogen atom suchas fluorine, chlorine, bromine or iodine; perhaloalkyl particularlyperhalo(C₁-C₆)alkyl such as fluoromethyl, difluoromethyl,trifluoromethyl, trifluoroethyl, fluoroethyl, difluoroethyl and thelike; substituted or unsubstituted (C₁-C₁₂)alkyl group, especially,linear or branched (C₁-C₈)alkyl group, such as methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl,iso-hexyl, heptyl, octyl and the like; cyclo(C₃-C₇)alkyl group such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, thecycloalkyl group may be substituted; cyclo(C₃-C₇)alkenyl group such ascyclopentenyl, cyclohexenyl, cycloheptynyl, cycloheptadienyl,cycloheptatrienyl and the like, the cycloalkenyl group may besubstituted; (C₁-C₁₂)alkoxy, especially, (C₁-C₆)alkoxy group such asmethoxy, ethoxy, propyloxy, butyloxy, iso-propyloxy and the like, whichmay be substituted; cyclo(C₃-C₇) alkoxy group such as cyclopropyloxy,cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and thelike, the cycloalkoxy group may be substituted; aryl group such asphenyl or naphthyl, the aryl group may be substituted; aralkyl groupsuch as benzyl, phenethyl, C₆H₅CH₂CH₂CH₂, naphthylmethyl and the like,the aralkyl group may be substituted and the substituted aralkyl is agroup such as CH₃C₆H₄CH₂, Hal-C₆H₄CH₂, CH₃OC₆H₄CH₂, CH₃OC₆H₄CH₂CH₂ andthe like; aralkoxy group such as benzyloxy, phenethyloxy,naphthylmethyloxy, phenylpropyloxy and the like, the aralkoxy group maybe substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl,morpholinyl, piperidinyl, piperazinyl and the like, the heterocyclylgroup may be substituted; heteroaryl group such as pyridyl, thienyl,furyl, pyrrolyl, oxazolyl, imidazolyl, oxadiazolyl, tetrazolyl,benzopyranyl, benzofuranyl and the like, the heteroaryl group may besubstituted; heterocyclo(C₁-C₆)alkyl, such as pyrrolidinealkyl,piperidinealkyl, morpholinealkyl, thiomorpholinealkyl, oxazolinealkyland the like, the heterocyclo(C₁-C₆)alkyl group may be substituted;heteroaralkyl group such as furanylmethyl, pyridinylmethyl,oxazolylmethyl, oxazolylethyl and the like, the heteroaralkyl group maybe substituted; heteroaryloxy, heteroaralkoxy, heterocycloalkoxy,wherein heteroaryl, heteroaralkyl, heterocycloalkyl andheterocyclylalkyl moieties are as defined earlier and may besubstituted; acyl groups such as acetyl, propionyl or benzoyl, the acylgroup may be substituted; acyloxy group such as CH₃COO, CH₃CH₂COO,C₆H₅COO and the like which may optionally be substituted, acylaminogroup such as CH₃CONH, CH₃CH₂CONH, C₃H₇CONH, C₆H₅CONH which may besubstituted, (C₁-C₆)monoalkylamino group such as CH₃NH, C₂H₅NH, C₃H₇NH,C₆H₁₃NH and the like, which may be substituted, (C₁-C₆)dialkylaminogroup such as N(CH₃)₂, CH₃(C₂H₅)N and the like, which may besubstituted; arylamino group such as C₆H₅NH, CH₃(C₆H₅)N, C₆H₄(CH₃)NH,NH—C₆H₄-Hal and the like, which may be substituted; arylalkylamino groupsuch as C₆H₅CH₂NH, C₆H₅CH₂CH₂NH, C₆H₅CH₂NCH₃ and the like, which may besubstituted; hydroxy(C₁-C₆)alkyl which may be substituted,amino(C₁-C₆)alkyl which may be substituted;mono(C₁-C₆)alkylamino(C₁-C₆)alkyl, di(C₁-C₆)alkylamino(C₁-C₆)alkyl groupwhich may be substituted, alkoxyalkyl group such as methoxymethyl,ethoxymethyl, methoxyethyl, ethoxyethyl and the like, which may besubstituted; aryloxyalkyl group such as C₆H₅OCH₂, C₆H₅OCH₂CH₂,naphthyloxymethyl and the like, which may be substituted; aralkoxyalkylgroup such as C₆H₅CH₂OCH₂, C₆H₅CH₂OCH₂CH₂ and the like, which may besubstituted; (C₁-C₆)alkylthio, thio(C₁-C₆)alkyl which may besubstituted, alkoxycarbonylamino group such as C₂H₅OCONH, CH₃OCONH andthe like which may be substituted; aryloxycarbonylamino group asC₂H₅OCONH, C₆H₅OCONCH₃, C₆H₅OCONC₂H₅, C₆H₅CH₅OCONH, C₆H₄(OCH₃)OCONH andthe like which may be substituted; aralkoxycarbonylamino group suchC₆H₅CH₂OCONH, C₆H₅CH₂CH₂OCONH, C₆H₅CH₂OCON(CH₃), C₆H₅CH₂OCON(C₂H₅),C₆H₄CH₃CH₂OCONH, C₆H₄OCH₃CH₂OCONH and the like, which may besubstituted; aminocarbonylamino group; (C₁-C₆)alkylaminocarbonylaminogroup, di(C₁-C₆)alkylaminocarbonylamino group; (C₁-C₆)alkylamidinogroup, (C₁-C₆)alkylguanidino, di(C₁-C₆)alkylguanidino groups, hydrazinoand hydroxylamino groups; carboxylic acid or its derivatives such asamides, like CONH₂, alkylaminocarbonyl like CH₃NHCO, (CH₃)₂NCO,C₂H₅NHCO, (C₂H₅)₂NCO, arylaminocarbonyl like PhNHCO, NapthylNHCO and thelike, aralkylaminocarbonyl such as PhCH₂NHCO, PhCH₂CH₂NHCO and the like,heteroarylaminocarbonyl and heteroaralkylamino carbonyl groups where theheteroaryl groups are as defined earlier, heterocyclylaminocarbonylwhere the heterocyclyl group is as defined earlier, carboxylic acidderivatives such as esters, wherein the ester moieties arealkoxycarbonyl groups such as unsubstituted or substitutedphenoxycarbonyl, naphthyloxycarbonyl and the like; aralkoxycarbonylgroup such as benzyloxycarbonyl, phenethyloxycarbonyl,naphthylmethoxycarbonyl and the like, heteroaryloxycarbonyl,heteroaralkoxycarbonyl, wherein the heteroaryl group is as definedearlier, heterocycloxycarbonyl where heterocycle is as defined earlierand these carboxylic acid derivatives may be substituted; sulfonic acidor its derivatives such as SO₂NH₂, SO₂NHCH₃, SO₂N(CH₃)₂, SO₂NHCF₃,SO₂NHCO(C₁-C₆)alkyl, SO₂NHCOaryl where the aryl group is as definedearlier and the sulfonic acid derivatives may be substituted; phosphoricacid and its derivatives as P(O)(OH)₂, P(O)OC₁-C₆-alkyl)₂, P(O)(O-aryl)₂and the like.

Suitable cyclic structures formed by the two adjacent groups like R₁ andR₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ and R₇ or R₇ and R₈ orR₈ and R₉ or R₁₁ and R₁₂ together with the carbon atoms to which theyare attached contain 5 to 6 ring atoms which may optionally contain oneor more heteroatoms selected from oxygen, nitrogen or sulfur andoptionally contain one or more double bonds and optionally containcombination of double bond and hetero atoms as described earlier. Thecyclic structures may be optionally substituted phenyl, naphthyl,pyridyl, furanyl, thienyl, pyrrolyl, imidazolyl, pyrimidinyl, pyrazinyland the like. Suitable substituents on the cyclic structure formed byR₁, and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ and R₇ or R₇ andR₈ or R₈ and R₉ or R₁₁ and R₁₂ together with the adjacent carbon atomsto which they are attached include oxo, hydroxy, halogen atom such aschlorine, bromine and iodine; nitro, cyano, amino, formyl, (C₁-C₃)alkyl,(C₁-C₃)alkoxy, thioalkyl, alkylthio phenyl or benzyl groups.

R₁₃ and R₁₄ preferably represents hydrogen, substituted or unsubstitutedlinear or branched (C₁-C₁₂)alkyl like methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, octyl and the like; arylgroup such as phenyl or naphthyl, the aryl group may be substituted;cyclo(C₃-C₇)alkyl group such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, the cycloalkyl group may be substituted; thearalkyl group may be substituted and the substituted aralkyl is a groupsuch as CH₃C₆H₄CH₂, Hal-C₆H₄CH₂, CH₃OC₆H₄CH₂(CH₃OC₆H₄CH₂CH₂ and thelike; (C₃-C₇)cycloheteroalkyl with heteroatoms like “Oxygen”, “Nitrogen”and “Sulfur” and optionally containing one or two double or triplebonds.

Suitable hetero cyclic rings formed by either R₁₁ and R₁₃ be selectedfrom pyrrolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyrrolidinyl,piperidinyl, morpholinyl, piperazinyl, oxazolinyl, diazolinyl and thelike, the heterocyclyl group may be substituted; heteroaryl group suchas pyridyl, pyrrolyl, oxazolyl, imidazolyl, oxadiazolyl, tetrazolyl,benzopyranyl and the like, the heteroaryl group may be substituted;heterocyclo(C₁-C₆)alkyl, such as pyrrolidinealkyl, piperidinealkyl,morpholinealkyl, thiomorpholinealkyl, oxazolinealkyl and the like, theheterocyclo(C₁-C₆)alkyl group may be substituted; heteroaralkyl groupsuch as furanmethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and thelike, the heteroaralkyl group may be substituted; heteroaryloxy,heteroaralkoxy, heterocycloalkoxy, wherein heteroaryl, heteroaralkyl,heterocycloalkyl and heterocyclylalkyl moieties are as defined earlierand may be further substituted.

Compounds of the present invention may be synthesized by syntheticroutes that include processes analogous to those known in the chemicalarts, particularly in light of the description contained herein. Thestarting materials are generally available from commercial sources suchas Aldrich Chemicals (Milwaukee, Wis.) or are readily prepared usingmethods well known to those skilled in the art (e.g., prepared bymethods generally described in Louis F. Fieser and Mary Fieser, Reagentsfor Organic Synthesis, v. 1-19, Wiley, New York (1967-1999 ed.), orBeilsteins Handbuch der organischen Chemie, 4, Aufl. ed.Springer-Verlag, Berlin, including supplements (also available via theBeilstein online database).

For illustrative purposes, the reaction schemes depicted below providepotential routes for synthesizing the compounds of the present inventionas well as key intermediates. For a more detailed description of theindividual reaction steps, see the Examples section. Those skilled inthe art will appreciate that other synthetic routes may be used tosynthesize the inventive compounds. Although specific starting materialsand reagents are depicted in the schemes and discussed below, otherstarting materials and reagents can be easily substituted to provide avariety of derivatives and/or reaction conditions. In addition, many ofthe compounds prepared by the methods described below can be furthermodified in light of this disclosure using conventional chemistry wellknown to those skilled in the art.

For example, a sulfide linkage (i.e., m=0) can be easily oxidized to itscorresponding sulfinyl or sulfonyl group (i.e., m=1 or m=2) using commonoxidation procedures (e.g., oxidation with m-chloroperbenzoic acid).Suitable values for Lg are for example, a halogeno, for example achloro, bromo, iodo, or aryl or alkyl sulfonyloxy group, for example, amethanesulfonyloxy or toluene-4-sulfonyloxy group or trifluoroacetate.

In the preparation of compounds of the present invention, protection ofremote functionality (e.g., primary or secondary amine) of intermediatesmay be necessary. The need for such protection will vary depending onthe nature of the remote functionality and the conditions of thepreparation methods. Suitable amino-protecting groups (NH-Pg) includetrifluoroacetyl, t-butoxycarbonyl (BOC), benzyloxycarbonyl (CBz) andFluorenylmethyleneoxycarbonyl (Fmoc). The need for such protection isreadily determined by one skilled in the art. For a general descriptionof protecting groups and their use, see T. W. Greene, Protective Groupsin Organic Synthesis, John Wiley & Sons, New York, 1991. The protectinggroups may be removed at a convenient subsequent stage using methodsknown from the art.

The present invention also provides processes for preparing compounds ofgeneral formula (I) as defined above their stereoisomers, theirpolymorphs, their pharmaceutically acceptable salts, theirpharmaceutically acceptable solvates and novel intermediates involvedtherein, which are as described below. There are few methods alreadyreported in the literature including GB patent specification 1 306 230,U.S. Pat. No. 3,509,163. These methods and references therein areincluded herein by reference.

In the description and the reaction scheme which follow R₁, R₂, R₃, R₄,R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃. R₁₄, m and n are as definedpreviously, while Lg, R, R_(a), R_(b) and R_(c) is as defined elsewherein the specification.

Scheme 1:

Compounds of general formula (I) may be prepared by reacting a compoundof formula (II) given below,

wherein R₁, R₂, R₃, R₄, and R₁₀ are as defined in relation to formula(I), further R₁₀ could be protected form thereof; R represents either ofa suitable N-protecting group, or a group such as,

wherein m, R₅, R₆, R₇. R₈ and R₉ are as defined earlier, with a compoundof formula (III) or its acid addition salt,

wherein n, R₁₁, R₁₂, R₁₃, and R₁₄ are as defined in relation to compoundof formula (I) or precursor thereof and Lg is a leaving group; andthereafter if necessary;

-   i) converting a compound of the formula (I) into another compound of    the formula (I)-   ii) removing any protecting groups; or    iii) forming a pharmaceutically acceptable salt, solvate or prodrug    thereof.

In case when R is a suitable protecting group, an additional step asdescribed in Scheme 2 is required to prepare compounds of formula (I).

The above reaction is preferably carried out in a solvent such as THF,toluene, acetone, ethyl acetate, DMF, DMSO, DME, N-methylpyrrolidone,methanol, ethanol propanol and the like and preferably using eitheracetone or DMF. The inert atmosphere may be maintained by using inertgases such as N₂, Ar or He. The reaction may be affected in the presenceof a base such as K₂CO₃, NaOH, Na₂CO₃, NaH and the like as well as themixtures thereof. The reaction mixture is generally heated to anelevated temperature or reflux temperature of the solvent, until thereaction is complete. A wide variety of basic agents can be used in thiscondensation. However, preferred basic agents are amines, such astrimethylamine, triethylamine, tributylamine, N-methylmorpholine,piperidine, N-methylpiperidine, pyridine and4-(N,N-dimethylamino)pyridine, with a preferred basic agent being K₂CO₃.Reaction times of about 30 minutes to 72 hours are common. At the end ofreaction, the volatile components are removed under reduced pressure.The reaction mixture can be optionally acidified before workup. Theproduct can be isolated by precipitation, washed, dried and furtherpurified by standard methods such as recrystallization, columnchromatography etc.

Optional step (i) and (ii) can be carried out using conventionalmethods. These will depend upon the precise nature of the substituentsR₁, R₂, R₃, R₄, R₁₀, R₁₁, R₁₂, R₁₃, and R₁₄ in each case. Examples ofsuitable reactions are illustrated hereinafter.

Scheme 2:

Alternatively, compounds of formula (I) may be prepared by reacting acompound of formula (IV) given below,

wherein n, R₁(R₂, R₃, R₄, R₁₁, R₁₂, R₁₃, and R₁₄ are as defined inrelation to formula (I), R₁₀ is as defined elsewhere in the definitionof compounds of formula (IV), with a compound of formula (V)

wherein m, R₅, R₆, R₇, R₈ and R₉, are as defined in relation to formula(I) and X is a halogen, preferably chloro or bromo; and thereafter ifdesired or necessary carrying out additional steps described above.

Compounds of formula (IV) and (V) are suitably reacted together in aninert organic solvent which includes, aromatic hydrocarbons such astoluene, o-, m-, p-xylene; halogenated hydrocarbons such as methylenechloride, chloroform, and chlorobenzene; ethers such as diethylether,diisopropyl ether, tert-butyl methyl ether, dioxane, anisole, andtetrahydrofuran; nitriles such as acetonitrile and propionitrile;ketones such as acetone, methyl ethyl ketone, diethyl ketone andtert-butyl methyl ketone; alcohols such as methanol, ethanol,n-propranol, n-butanol, tert-butanol and also DMF(N,N-dimethylformamide), DMSO(N,N-dimethyl sulfoxide) and water. Thepreferred list of solvents includes DMSO, DMF, acetonitrile and THF.Mixtures of these in varying ratios can also be used. Suitable basesare, generally, inorganic compounds such as alkali metal hydroxides andalkaline earth metal hydroxides, such as lithium hydroxide, sodiumhydroxide, potassium hydroxide and calcium hydroxide; alkali metaloxides and alkaline earth metal oxides, lithium oxide, sodium oxide,magnesium oxide and calcium oxide; alkali metal hydrides and alkalineearth metal hydrides such as lithium hydride, sodium hydride, potassiumhydride and calcium hydride; alkali metal amides and alkaline earthmetal amides such as lithium amide, sodium amide, potassium amide andcalcium amide; alkali metal carbonates and alkaline earth metalcarbonates such as lithium carbonate and calcium carbonate; and alsoalkali metal hydrogen carbonates and alkaline earth metal hydrogencarbonates such as sodium hydrogen carbonate; organometallic compounds,particularly alkali-metal alkyls such as methyl lithium, butyl lithium,phenyl lithium; alkyl magnesium halides such as methyl magnesiumchloride, and alkali metal alkoxides and alkaline earth metal alkoxidessuch as sodium methoxide, sodium ethoxide, potassium ethoxide, potassiumtert-butoxide and di-methoxymagnesium, further more organic bases e.g.triethylamine, triisopropylamine, and N-methylpiperidine, pyridine.Sodium hydroxide, Sodium methoxide, Sodium ethoxide, potassium hydroxidepotassium carbonate and triethylamine are especially preferred. Suitablythe reaction may be effected in the presence of phase transfer catalystsuch as tetra-n-butylammonium hydrogensulphate and the like. The inertatmosphere may be maintained by using inert gases such as N₂, Ar or He.Reaction times may vary from 1 to 24 hrs, preferably from 2 to 6 hours,whereafter, if desired, the resulting compound is continued into a saltthereof.

Compounds of formula (IV) may be prepared as reported in the literatureor by the method analogous to that described in Scheme 1, between thecompound of formula (II) and (III), wherein ring nitrogen is protectedbefore the reaction.

Scheme 3:

Alternatively, compounds of formula (I) may be prepared by reacting acompound of formula (VI)

wherein R₁, R₂, R₃, R₄ and R₁₀ are as defined in relation to formula(I), R₁₀ could also be protected form thereof; R_(a) is defined aseither hydrogen, halogen (such as chloro or bromo), lithio,trimethylsilyl, lower alkoxy, boronic acid or trifluoromethanesulfonategroups; R is defined as a suitable N-protecting group or a group suchas,

wherein m, R₅, R₅, R₇, R₈ and R₉ are as defined earlier for compound offormula (I), and with a compound of formula (III) or its acid additionsalt

wherein n, R₁₁, R₁₂, R₁₃, and R₁₄ are as defined in relation to compoundof formula (I) or precursor thereof and Lg is a leaving group; or itsacid addition salt of compound of formula (III) may be used; andthereafter if desired or necessary carrying out additional stepsdescribed above.

Suitable substituents for Lg is either a hydroxy, sulfonyloxy group or ahalogeno as defined earlier and the selection is based upon the natureof substitution at R_(a). Whenever R is acetyl, an additional stepdescribed in Scheme 2 is required to prepare compounds of generalformula (I).

The above reaction is preferably carried out in a solvent such as THF,toluene, ethyl acetate, acetone, water, DMF, DMSO, DME, and the like ora mixture thereof, and preferably using either acetone or DMF. The inertatmosphere may be maintained by using inert gases such as N₂, Ar or He.The reaction may be affected in the presence of a base such as K₂CO₃,Na₂CO₃, NaH or mixtures thereof. The reaction temperature may range from20° C. to 150° C. based on the choice of solvent and preferably at atemperature in the range from 30° C. to 100° C. The duration of thereaction may range from 1 to 24 hours, preferably from 2 to 6 hours.

Scheme 4:

Alternatively, compounds of formula (I) may be prepared by reacting acompound of formula (VII)

wherein R₁, R₂, R₃, R₄, R₁₀, R₁₁ and R₁₂ are as defined in relation toformula (I), R₁₀ is a group R₁₀ as defined in relation to formula (I) orprotected form thereof; R is defined as a suitable N-protecting group,or a group such as,

wherein m, R₅, R₆, R₇, R₈ and R₉ are as defined earlier for compound offormula (I), with a compound of formula (VIII)NR₁₃R₁₄H  (VIII)wherein R₁₃ and R₁₄ are as defined in relation to compound of formula(I) or precursor thereof or with its acid addition salt thereof; andthereafter if desired or necessary carrying out additional stepsdescribed above.

Suitable values for Lg are for example, a halogeno or sulfonyloxy group,for example a chloro, bromo, iodo, methanesulfonyloxy ortoluene-4-sulfonyloxy group or trifluoroacetyl.

Scheme 5:

Alternatively, compounds of formula (I) may be prepared by reductivealkylation of compounds of formula (IX)

wherein n, R₁, R₂, R₃, R₄, R₁₀, R₁₁ and R₁₂ are as defined in relationto formula (I), R₁₀ could also be a protected form thereof; R is definedas a suitable N-protecting group or a group such as,

wherein m, R₅, R₆, R₇, R₈ and R₉ are as defined earlier for compound offormula (I), with a compound of formula (VIII)NR₁₃R₁₄H  (VIII)wherein R₁₃ and R₁₄ are as defined in relation to compound of formula(I) or precursor thereof or with its acid addition salt thereof; andthereafter if desired or necessary carrying out additional stepsdescribed above.Scheme 6:

Alternatively, compounds of formula (I) in which R₁₃ is lower alkylradical such as C₁₋₆alkyl, a cycloalkyl containing 3-8 carbon atoms or abenzyl radical in which phenyl ring is substituted and R₁₄ is hydrogenmay be prepared from another compound of formula (X)

Where n, R₁, R₂, R₃, R₄, R₁₀, R₁₁ and R₁₂ are as defined in relation toformula (I), R₁₀ is a group R₁₀ as defined in relation to formula (I) orprotected form thereof; and in which R_(b) represents hydrogen atom or abenzyl group in which phenyl ring is substituted and removable byhydrogenolysis, R is defined as a suitable N-protecting group or a groupsuch as,

wherein m, R₅, R₆, R₇, R₈ and R₉ are as defined earlier for compound offormula (I), with a compound of formula (XI)

wherein R₁₃ and R₁₄ are as defined in relation to compound of formula(I) or precursor thereof or with its acid addition salt thereof; andthereafter if desired or necessary carrying out additional stepsdescribed above.

Similarly, when R₁₀, R₁₃ and R₁₄ represents hydrogen atoms, thesecompounds may be prepared according to this invention by hydrogenolysingthe corresponding indole derivative, in which above substituentsrepresent one or more benzyl groups removable by hydrogenolysis.

Furthermore, indole derivatives of the general formula (I) in which R₁₃is benzyl or a substituted benzyl group removable by hydrogenolysis andR₁₄ is hydrogen, may according to this invention be prepared bypartially hydrogenolysing the corresponding indole derivative in whichR₁₄ is identical to the substitutent R₁₃ above. The said hydrogenolysisis performed in a solvent such as ethanol in the presence of a suitablecatalyst, e.g. palladium on carbon. The reaction is performed in asolvent such as methanol or ethanol in the presence of hydrogen and asuitable catalyst such as palladium on carbon.

Novel intermediates of general formula (II) are represented as givenbelow,

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈ and R₉ may be same or different,and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio, amino,nitro, cyano, formyl, amidino, guanidino, substituted or unsubstitutedgroups selected from linear or branched (C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl,(C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl, (C₃-C₇)cycloalkenyl, bicycloalkyl,bicycloalkenyl, (C₁-C₁₂)alkoxy, cyclo(C₃-C₇)alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heterocyclyl, heteroaryl, heterocyclylalkyl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, heterocyclylalkyloxy,acyl, acyloxy, acylamino, monoalkylamino, dialkylamino, arylamino,diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl,aralkoxycarbonyl, heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl,hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl,alkoxyalkyl arylalkyl, aralkoxyalkyl, alkylthio, thioalkyl,alkoxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, hydroxylamino, carboxylic acid and its derivatives, sulfonicacids and its derivatives, phosphoric acid and its derivatives; or theadjacent groups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ orR₆ and R₇ or R₇ and R₈ or R₈ and R₉ together with carbon atoms to whichthey are attached may form a five or a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; “m” is an integer ranging from 0 to 2 preferably m is 1or 2; R₁₀ represents hydrogen, halogen, perhaloalkyl, substituted orunsubstituted groups selected from linear or branched (C₁-C₃)alkyl andaryl; and its stereoisomers and its salts

Numerous processes to prepare the compounds of formula (II) can be foundin literature. Some of them are J. Heterocyclic Chemistry, 16, 221(1979), JP patent publication 57200362 A, U.S. Pat. No. 3,860,608 and DE111890. Alternatively, compounds of formula (II) may suitably beprepared by conventional methods for oxidization ofindole-3-carboxaldehydes as described in literature (Chem. Pharm. Bull,1985, 33, 1843, wherein HMPA, mCPBA are used as oxidizing agent).

Novel intermediates of general formula (VI) are represented as givenbelow.

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈ and R₉ may be same or different,and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio, amino,nitro, cyano, formyl, amidino, guanidino, substituted or unsubstitutedgroups selected from linear or branched (C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl,(C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl, (C₃-C₇)cycloalkenyl, bicycloalkyl,bicycloalkenyl, (C₁-C₁₂)alkoxy, cyclo(C₃-C₇)alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heterocyclyl, heteroaryl, heterocyclylalkyl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, heterocyclylalkyloxy,acyl, acyloxy, acylamino, monoalkylamino, dialkylamino, arylamino,diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl,aralkoxycarbonyl, heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl,hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl,alkoxyalkyl arylalkyl, aralkoxyalkyl, alkylthio, thioalkyl,alkoxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, hydroxylamino, carboxylic acid and its derivatives, sulfonicacids and its derivatives, phosphoric acid and its derivatives; or theadjacent groups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ orR₆ and R₇ or R₇ and R₈ or R₈ and R₉ together with carbon atoms to whichthey are attached may form a five or a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; and “m” is an integer ranging from 0 to 2 preferably mis 1 or 2; R₁₀ represents hydrogen, halogen, perhaloalkyl, substitutedor unsubstituted groups selected from linear or branched (C₁-C₃)alkyland aryl;R_(a) is defined as either hydrogen, halogen (such as chloro or bromo),lithio, trimethylsilyl, lower alkoxy, boronic acid ortrifluoromethanesulfonate groups; and its stereoisomers and its salts;along with the proviso that whenever R is SO₂Ph, and all of R₁, R₂, R₃,R₄, R₅, R₆, R₇, R₈, R₉ and R₁₀ substituents are hydrogen's R_(a) nevereither of bromo, lithio, trimethylsilyl, boronic acid ortrifluoromethanesulfonate groups.

Procedure to prepare compounds of formula (VI) is as reported inHeterocycles, vol. 30, no. 1, 1990.

Novel intermediates of general formula (VII) are represented as givenbelow,

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₁ and R₁₂ may be same ordifferent, and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio,amino, nitro, cyano, formyl, amidino, guanidino, substituted orunsubstituted groups selected from linear or branched (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, (C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl,(C₃-C₇)cycloalkenyl, bicycloalkyl, bicycloalkenyl, (C₁-C₁₂)alkoxy,cyclo(C₃-C₇)alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl,heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino,alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl,aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkoxyalkylarylalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino,aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino,alkylamidino, alkylguanidino, dialkylguanidino, hydrazino,hydroxylamino, carboxylic acid and its derivatives, sulfonic acids andits derivatives, phosphoric acid and its derivatives; or the adjacentgroups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ andR₇ or R₇ and R₈ or R₈ and R₉ together with carbon atoms to which theyare attached may form a five or a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; or R₁₁ and R₁₂ together with carbon atoms to which theyare attached may form a three to a six membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; R₁₀ represents hydrogen, halogen, perhaloalkyl,substituted or unsubstituted groups selected from linear or branched(C₁-C₃)alkyl and aryl; “n” is an integer ranging from 1 to 8, preferably1 to 4, wherein the carbon chains which “n” represents may be eitherlinear or branched; and V is an integer ranging from 0 to 2 preferably mis 1 or 2; and Lg is a leaving group as defined earlier and itsstereoisomers and its salts.

Novel intermediates of general formula (IX) are represented as givenbelow,

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₁ and R₁₂ may be same ordifferent, and represent hydrogen, halogen, perhaloalkyl, hydroxy, thio,amino, nitro, cyano, formyl, amidino, guanidino, substituted orunsubstituted groups selected from linear or branched (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, (C₂-C₁₂)alkynyl, (C₃-C₇)cycloalkyl,(C₃-C₇)cycloalkenyl, bicycloalkyl, bicycloalkenyl, (C₁-C₁₂)alkoxy,cyclo(C₃-C₇)alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl,heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino,alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl,aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkoxyalkylarylalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino,aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino,alkylamidino, alkylguanidino, dialkylguanidino, hydrazino,hydroxylamino, carboxylic acid and its derivatives, sulfonic acids andits derivatives, phosphoric acid and its derivatives; or the adjacentgroups like R₁ and R₂ or R₂ and R₃ or R₃ and R₄ or R₅ and R₆ or R₆ andR₇ or R₇ and R₈ or R₈ and R₉ together with carbon atoms to which theyare attached may form a five or a sue membered ring, optionallycontaining one or more double bonds and optionally containing one ormore heteroatoms selected from O, N, S and combinations of double bondand heteroatoms; R₁₀ represents hydrogen, halogen, perhaloalkyl,substituted or unsubstituted groups selected from linear or branched(C₁-C₃)alkyl and aryl; “n” is an integer ranging from 1 to 8, preferably1 to 4, wherein the carbon chains which “n” represents may be eitherlinear or branched; and “m” is an integer ranging from 0 to 2 preferablym is 1 or 2 and its stereoisomers and its salts.

The stereoisomers of compounds of general formula (I) may be prepared byone or more ways presented below:

-   i) One or more of the reagents may be used in their optically active    form.-   ii) Optically pure catalyst or chiral ligands along with metal    catalyst may be employed in the reduction process. The metal    catalysts may be employed in the reduction process. The metal    catalyst may be Rhodium, Ruthenium, Indium and the like. The chiral    ligands may preferably be chiral phosphines (Principles of    Asymmetric synthesis, J. E. Baldwin Ed., Tetrahedron series, 14,    311-316).-   iii) The mixture of stereoisomers may be resolved by conventional    methods such as forming a diastereomeric salts with chiral acids or    chiral amines, or chiral amino alcohols, chiral amino acids. The    resulting mixture of diastereomers may then be separated by methods    such as fractional crystallization, chromatography and the like,    which is followed by an additional step of isolating the optically    active product by hydrolyzing the derivative (Jacques et. al.,    “Enantiomers, Racemates and Resolution”, Wiley Interscience, 1981).-   iv) The mixture of stereoisomers may be resolved by conventional    methods such as microbial resolution, resolving the diastereomeric    salts formed with chiral acids or chiral bases.

Chiral acids that can be employed may be tartaric acid, mandelic acid,lactic acid, camphorsulfonic acid, amino acids and the like. Chiralbases that can be employed may be cinchona alkaloids, brucine or a basicamino group such as lysine, arginine and the like.

Isotopically labelled compounds of the present invention are useful indrug and/or substrate tissue distribution and target occupancy assays.For example, isotopically labelled compounds are particularly useful inSPECT (single photon emission computed tomography) and in PET (positronemission tomography).

The pharmaceutically acceptable salts forming a part of this inventionmay be prepared by treating the compound of formula (I) with 1-6equivalents of a base such as sodium hydride, sodium methoxide, sodiumethoxide, sodium hydroxide, potassium t-butoxide, calcium hydroxide,calcium acetate, calcium chloride, magnesium hydroxide, magnesiumchloride and the like. Solvents such as water, acetone, ether, THF,methanol, ethanol, t-butanol, dioxane, isopropanol, isopropyl ether ormixtures thereof may be used. Organic bases such lysine, arginine,methyl benzylamine, ethanolamine, diethanolamine, tromethamine, choline,guanidine and their derivatives may be used. Acid addition salts,wherever applicable may be prepared by treatment with acids such astartaric acid, mandelic acid, fumaric acid, maleic acid, lactic acid,salicyclic acid, citric acid, ascorbic acid, benzene sulfonic acid,p-toluene sulfonic acid, hydroxynaphthoic acid, methane sulfonic acid,malic acid, acetic acid, benzoic acid, succinic acid, palmitic acid,oxalic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitricacid and the like in solvents such as water, alcohols, ethers, ethylacetate, dioxane, DMF or a lower alkyl ketone such as acetone, or themixtures thereof.

Different polymorphs may be prepared by crystallization of compounds ofgeneral formula (I) under different conditions such as differentsolvents or solvent mixtures in varying proportions forrecrystallization, various ways of crystallization such as slow cooling,fast cooling or a very fast cooling or a gradual cooling duringcrystallization. Also heating the compound, melting the compound andsolidification by gradual or fast cooling, heating or melting undervacuum or under inert atmosphere, and cooling under either vacuum orinert atmosphere. Either one or more of the following techniques such asdifferential scanning calorimeter, powder X-ray diffraction, IRspectroscopy, solid probe NMR spectroscopy and thermal microscopy canidentify the polymorphs thus prepared.

The pharmaceutical compositions of the present invention may beformulated in a conventional manner using one or more pharmaceuticallyacceptable carriers. Thus, the active compounds of the invention may beformulated for oral, buccal, intranasal, parental (e.g., intravenous,intramuscular or subcutaneous) or rectal administration or a formsuitable for administration by inhalation or insufflation.

“Therapeutically effective amount” is defined an ‘amount of a compoundof the present invention that (i) treats or prevents the particulardisease, condition, or disorder, (ii) attenuates, ameliorates, oreliminates one or more symptoms of the particular disease, condition, ordisorder, or (iii) prevents or delays the onset of one or more symptomsof the particular disease, condition, or disorder described herein’.

The dose of the active compounds can vary depending on factors such asthe route of administration, age and weight of patient, nature andseverity of the disease to be treated and similar factors. Therefore,any reference herein to a pharmacologically effective amount of thecompounds of general formula (I) refers to the aforementioned factors. Aproposed dose of the active compounds of this invention, for eitheroral, parenteral, nasal or buccal administration, to an average adulthuman, for the treatment of the conditions referred to above, is 0.1 to200 mg of the active ingredient per unit dose which could beadministered, for example, 1 to 4 times per day.

For oral administration, the pharmaceutical compositions may take theform of, for example, tablets or capsules prepared by conventional meanswith pharmaceutically acceptable excipients such as binding agents(e.g., pregelatinised maize starch, polyvinylpyrrolidone orhydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystallinecellulose or calcium phosphate); lubricants (e.g., magnesium stearate,talc or silica); disintegrants (e.g., potato starch or sodium starchglycolate); or wetting agents (e.g., sodium lauryl sulphate). Thetablets may be coated by methods well known in the art. Liquidpreparations for oral administration may take the form of, for example,solutions, syrups or suspensions, or they may be presented as a dryproduct for constitution with water or other suitable vehicle beforeuse. Such liquid preparations may be prepared by conventional means withpharmaceutically acceptable additives such as suspending agents (e.g.,sorbitol syrup, methyl cellulose or hydrogenated edible fats);emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles(e.g., almond oil, oily esters or ethyl alcohol); and preservatives(e.g., methyl or propyl p-hydroxybenzoates or sorbic acid).

For buccal administration, the composition may take the form of tabletsor lozenges formulated in conventional manner.

The active compounds of the invention may be formulated for parenteraladministration by injection, including using conventionalcatheterization techniques or infusion. Formulations for injection maybe presented in unit dosage form, e.g., in ampules or in multi-dosecontainers, with an added preservative. The compositions may take suchforms as suspensions, solutions or emulsions in oily or aqueousvehicles, and may contain formulating agents such as suspending,stabilizing and/or dispersing agents. Alternatively, the activeingredient may be in powder form for reconstitution with a suitablevehicle, e.g., sterile pyrogen-free water, before use.

The active compounds of the invention may also be formulated in rectalcompositions such as suppositories or retention enemas, e.g., containingconventional suppository bases such as cocoa butter or other glycerides.

For intranasal administration or administration by inhalation, theactive compounds of the invention are conveniently delivered in the formof an aerosol spray from a pressurized container or a nebulizer, or froma capsule using a inhaler or insufflator. In the case of a pressurizedaerosol, a suitable propellant, e.g., dichlorodifluoromethane,trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide orother suitable gas and the dosage unit may be determined by providing avalve to deliver a metered amount. The medicament for pressurizedcontainer or nebulizer may contain a solution or suspension of theactive compound while for a capsule it preferably should be in the formof powder. Capsules and cartridges (made, for example, from gelatin) foruse in an inhaler or insufflator may be formulated containing a powdermix of a compound of the invention and a suitable powder base such aslactose or starch.

Aerosol formulations for treatment of the conditions referred to above(e.g., migraine) in the average adult human are preferably arranged sothat each metered dose or “puff” of aerosol contains 20 μg to 1000 μg ofthe compound of the invention. The overall daily dose with an aerosolwill be within the range 100 μg to 10 mg. Administration may be severaltimes daily, for example 2, 3, 4 or 8 times, giving for example, 1, 2 or3 doses each time.

The affinities of the compound of this invention for the variousserotonin receptors are evaluated using standard radioligand bindingassays and are described here.

Radioligand Binding Assays for Various 5-HT Receptor Sub-Types:

i) Assay for 5HT_(1A)

Materials and Methods:

Receptor source: Human recombinant expressed in HEK-293 cells

Radioligand: [3H]-8-OH-DPAT (221 Ci/mmol)

Final ligand concentration—[0.5 nM]

Reference compound: 8-OH-DPAT

Positive control: 8-OH-DPAT

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mMMgSO₄, 0.5 mM EDTA and 0.1% Ascorbic acid at room temperature for 1hour. The reaction is terminated by rapid vacuum filtration onto glassfiber filters. Radioactivity trapped onto the filters is determined andcompared to control values in order to ascertain any interactions oftest compound with the 5HT_(1A) binding site.

Literature Reference:

-   Hoyer D., Engel G., et al. Molecular Pharmacology of 5HT₁ and 5-HT₂    Recognition Sites in Rat and Pig Brain Membranes: Radioligand    Binding Studies with [³H]-5HT, [³H]-8-OH-DPAT,    [¹²⁵I]-Iodocyanopindolol, [³H]-Mesulergine and [³H]-Ketanserin. Eur.    Jml. Pharmacol. 118: 13-23 (1985) with modifications.-   Schoeffter P. and Hoyer D. How Selective is GR 43175? Interactions    with Functional 5-HT_(1A), 5HT_(1B), 5-HT_(1C), and 5-HT_(1D)    Receptors. Naunyn-Schmiedeberg's Arch. Pharmac. 340: 135-138 (1989)    with modifications.    ii) Assay for 5HT_(1B)    Materials and Methods:

Receptor source: Rat striatal membranes

Radioligand: [¹²⁵I]Iodocyanopindolol (2200 Ci/mmol)

Final ligand concentration—[0.15 nM]

Non-specific determinant: Serotonin—[10 μM]

Reference compound: Serotonin

Positive control: Serotonin

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 60 μM(−) isoproterenol at 37° C. for 60 minutes. The reaction is terminatedby rapid vacuum filtration onto glass fiber filters. Radioactivitytrapped onto the filters is determined and compared to control values inorder to ascertain any interactions of test compound with the 5HT_(1B)binding site.

Literature Reference:

-   Hoyer D., Engel G., et al. Molecular Pharmacology of 5HT₁ and 5-HT₂    Recognition Sites in Rat and Pig Brain Membranes: Radioligand    Binding Studies with [³H]-5HT, [³H]-8-OH-DPAT,    [¹²⁵I]-Iodocyanopindolol, [³H]-Mesulergine and [³H]-Ketanserin. Eur.    Jml. Pharmacol. 118: 13-23 (1985) with modifications.-   Schoeffter P. and Hoyer D. How selective is GR 43175? Interactions    with Functional 5-HT_(1A), 5HT_(1B), 5-HT_(1C), and 5-HT₁ Receptors.    Naunyn-Schmiedeberg's Arch. Pharmac. 340: 135-138 (1989) with    modifications.    iii) Assay for 5HT_(1D)    Materials and Methods:

Receptor source: Human cortex

Radioligand: [³H] 5-Carboxamidotryptamine (20-70 Ci/mmol)

Final ligand concentration—[2.0 nM]

Non-specific determinant: 5-Carboxamidotryptamine (5-CT)-[1.0 μM]

Reference compound: 5-Carboxamidotryptamine (5-CT)

Positive control: 5-Carboxamidotryptamine (5-CT)

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.7) containing 4 mMCaCl₂, 100 nM 8-OH-DPAT, 100 nM Mesulergine, 10 uM Pargyline and 0.1%ascorbic acid at 25° C. for 60 minutes. The reaction is terminated byrapid vacuum filtration onto glass fiber filters. Radioactivity trappedonto the filters is determined and compared to control values in orderto ascertain any interactions of test compound with the cloned 5HT_(1D)binding site.

Literature Reference:

-   Waeber C, Schoeffter, Palacios J. M. and Hoyer D. Molecular    Pharmacology of the 5-HT_(1D) Recognition Sites: Radioligand Binding    Studies in Human, Pig, and Calf Brain Membranes.    Naunyn-Schmiedeberg's Arch. Pharmacol. 337: 595-601 (1988) with    modifications.    iv) Assay for 5HT_(2A)    Materials and Methods:

Receptor source: Human Cortex

Radioligand: [³H] Ketanserin (60-90 Ci/mmol)

Final ligand concentration—[2.0 nM]

Non-specific determinant: Ketanserin—[3.0 μM]

Reference compound: Ketanserin

Positive control: Ketanserin

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.5) at room temperaturefor 90 minutes. The reaction is terminated by rapid vacuum filtrationonto glass fiber filters. Radioactivity trapped onto the filters isdetermined and compared to control values in order to ascertain anyinteractions of test compound with the 5HT_(2A) binding site.

Literature Reference:

-   Leysen J. E., Niemegeers C. J., Van Nueten J. M. and Laduron P. M.    [³H]Ketanserin: A Selective Tritiated Ligand for Serotonin₂ Receptor    Binding Sites. Mol. Pharmacol. 21: 301-314 (1982) with    modifications.-   Martin, G. R. and Humphrey, P. P. A. Classification Review:    Receptors for 5-HT: Current Perspectives on Classification and    Nomenclature. Neuropharmacol. 33(3/4): 261-273 (1994).    v) Assay for 5HT_(2C)    Materials and Methods:

Receptor source: Pig choroid plexus membranes

Radioligand: [³H] Mesulergine (50-60 Ci/mmol)

Final ligand concentration—[1.0 nM]

Non-specific determinant: Serotonin—[100 nM]

Reference compound: Mianserin

Positive control: Mianserin

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.7) containing 4 mMCaCl₂ and 0.1% ascorbic acid at 37° C. for 60 minutes. The reaction isterminated by rapid vacuum filtration onto glass fiber filters.Radioactivity trapped onto the filters is determined and compared tocontrol values in order to ascertain any interactions of test compoundwith the 5HT_(2C) binding site.

Literature Reference:

-   A. Pazos, D. Hoyer, and J. Palacios. The Binding of Serotonergic    Ligands to the Porcine Choroid Plexus: Characterization of a New    Type of Serotonin Recognition Site. Eur. Jml. Pharmacol. 106:    539-546 (1985) with modifications.-   Hoyer, D., Engel, G., et al. Molecular Pharmacology of 5HT₁ and    5-HT₂ Recognition Sites in Rat and Pig Brain Membranes: Radioligand    Binding Studies with [3H]-5HT, [3H]-8-OH-DPAT,    [¹²⁵I]-Iodocyanopindolol, [3H]-Mesulergine and [3H]-Ketanserin. Eur.    Jml. Pharmacol. 118: 13-23 (1985) with modifications.    vi) Assay for 5HT₃    Materials and Methods:

Receptor source: N1E-115 cells

Radioligand: [³H]-GR 65630 (30-70 Ci/mmol)

Final ligand concentration—[0.35 nM]

Non-specific determinant: MDL-72222—[1.0 μM]

Reference compound: MDL-72222

Positive control: MDL-72222

Incubation Conditions:

Reactions are carried out in 20 mM HEPES (pH 7.4) containing 150 mM NaClat 25° C. for 60 minutes. The reaction is terminated by rapid vacuumfiltration onto glass fiber filters. Radioactivity trapped onto thefilters is determined and compared to control values in order toascertain any interactions of test compound with the 5HT₃ binding site.

Literature Reference:

-   Lummis S. C. R., Kilpatrick G. J. Characterization of 5HT₃ Receptors    in intact N1E-115 Neuroblastoma Cells. Eur. Jml. Pharmacol. 189:    223-227 (1990) with modifications.-   Hoyer D. and Neijt H. C. Identification of Serotonin 5-HT₃    Recognition Sites in Membranes of N1E-115 Neuroblastoma Cells by    Radioligand Binding. Mol. Pharmacol. 33: 303 (1988).-   Tyers M. B. 5-HT₃ Receptors and the Therapeutic Potential of 5HT₃    Receptor Antagonists. Therapie. 46:431-435 (1991).    vii) Assay for 5HT₄    Materials and Methods:

Receptor source: Guinea pig striatal membranes

Radioligand: [³H] GR-113808 (30-70 Ci/mmol)

Final ligand concentration—[0.2 nM]

Non-specific determinant: Serotonin (5-HT)-[30 μM]

Reference compound: Serotonin (5-HT)

Positive control: Serotonin (5-HT)

Incubation Conditions:

Reactions are carried out in 50 mM HEPES (pH 7.4) at 370C for 60minutes. The reaction is terminated by rapid vacuum filtration ontoglass fiber filters. Radioactivity trapped onto the filters isdetermined and compared to control values in order to ascertain anyinteractions of test compound with the 5HT₄ binding site.

Literature Reference:

-   Grossman Kilpatrick, C, et al. Development of a Radioligand Binding    Assay for 5HT₄ Receptors in Guinea Pig and Rat Brain. Brit. J    Pharmco. 109: 618-624 (1993).    viii) Assay for 5HT_(5A)    Materials and Methods:

Receptor source: Human recombinant expressed in HEK 293 cells

Radioligand: [³H] LSD (60-87 Ci/mmol)

Final ligand concentration—[1.0 nM]

Non-specific determinant: Methiothepin mesylate—[1.0 μM]

Reference compound: Methiothepin mesylate

Positive control: Methiothepin mesylate

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mMMgSO₄ and 0.5 mM EDTA at 37° C. for 60 minutes. The reaction isterminated by rapid vacuum filtration onto glass fiber filters.Radioactivity trapped onto the filters is determined and compared tocontrol values in order to ascertain any interactions of test compoundwith the cloned 5HT_(5A) binding site.

Literature Reference:

-   Rees S., et al. FEBS Letters, 355: 242-246 (1994) with modifications    ix) Assay for 5HT₆    Materials and Methods:

Receptor source: Human recombinant expressed in HEK293 cells

Radioligand: [³H] LSD (60-80 Ci/mmol)

Final ligand concentration—[1.5 nM]

Non-specific determinant: Methiothepin mesylate—[0.1 μM]

Reference compound: Methiothepin mesylate

Positive control: Methiothepin mesylate

Incubation Conditions:

Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mMMgCl₂, 0.5 mM EDTA for 60 minutes at 37° C. The reaction is terminatedby rapid vacuum filtration onto glass fiber filters. Radioactivitytrapped onto the filters is determined and compared to control values inorder to ascertain any interactions of test compound(s) with the clonedserotonin—5HT₆-binding site.

Literature Reference:

-   Monsma F. J. Jr., et al., Molecular Cloning and Expression of Novel    Serotonin Receptor with High Affinity for Tricyclic Psychotropic    Drugs. Mol. Pharmacol. (43): 320-327 (1993).    x) Assay for 5-HT₇    Materials and Methods:

Receptor source: Human recombinant expressed in CHO cells

Radioligand: [³H] LSD (60-80 Ci/mmol)

Final ligand concentration—[2.5 nM]

Non-specific determinant: 5-Carboxamidotryptamine (5-CT)-[0.1 μM]

Reference compound: 5-Carboxamidotryptamine

Positive control: 5-Carboxamidotryptamine

Incubation Conditions:

Reactions are earned out in 50 mM TRIS-HCl (pH 7.4) containing 10 mMMgCl₂, 0.5 mM EDTA for 60 minutes at 37° C. The reaction is terminatedby rapid vacuum filtration onto glass fiber filters. Radioactivitytrapped onto the filters is determined and compared to control values inorder to ascertain any interactions of test compound(s) with the clonedserotonin—5HT₇-binding site.

Literature Reference:

-   Y. Shen, E. Monsma, M. Metcalf, P. Jose, M Hamblin, D. Sibley,    Molecular Cloning and Expression of a 5-hydroxytryptamine-7    Serotonin Receptor Subtype. J. Biol. Chem. 268: 18200-18204.

The following description illustrates the method of preparation ofvariously substituted compounds of general formula (I), according to themethods described herein. These are provided by the way of illustrationonly and therefore should not be construed to limit the scope of theinvention.

Commercial reagents were utilized without further purification. Roomtemperature refers to 25-30° C. Melting points are uncorrected. IRspectra were taken using KBr and in solid state. Unless otherwisestated, all mass spectra were carried out using ESI conditions. 1H NMRspectra were recorded at 200 MHz on a Bruker instrument. Deuteratedchloroform (99.8% D) was used as solvent. TMS was used as internalreference standard. Chemical shift values are expressed in are reportedin parts per million (δ)-values. The following abbreviations are usedfor the multiplicity for the NMR signals: s=singlet, bs=broad singlet,d=doublet, t=triplet, q=quartet, qui=quintet, h=heptet, dd=doubledoublet, dt=double triplet, tt=triplet of triplets, m=multiplet. NMR,mass were corrected for background peaks. Specific rotations weremeasured at room temperature using the sodium D (589 nm). Chromatographyrefers to column chromatography performed using 60-120 mesh silica geland executed under nitrogen pressure (flash chromatography) conditions.

Description 1: General Procedure for the Preparation of MonoperphthalicAcid (D 1)

To the mixture containing phthalic anhydride (2.22 g, 0.015 mole) anddiethyl ether (25 mL), hydrogen peroxide solution (3.4 g; 0.03 moles; as30% aqueous solution) was added and the reaction mixture was stirred at25° C. to dissolve the anhydride. The reaction mixture was transferredto a separating funnel, ether layer was separated and aqueous layer wasextracted with ether (3×10 mL). Combined ether extracts are dried oversodium sulfate and this solution of monoperphthalic acid was used.

Description 2: 1-Benzenesulfonyl-2-phenyl-1H-indole (D 2)

Route I:

In a three-necked round bottom flask equipped with pressure equalizingfunnel, sodium hydride (0.6 g of 50% in mineral oil; 0.0125 mole) andDMF (8 mL) were taken. 2-Phenyl-1H-indole (0.01 mole) was added slowlyat 0° C. and the reaction mixture was stirred well. Then it was warmedto 25° C. and stirring was continued for one hour. Afterwards, thereaction mixture was cooled and Benzenesulfonyl chloride (2.1 g; 0.012mole in 5 mL) was added slowly from the pressure equalizing funnel overminutes, and further stirred at 25° C. for 3 hours. After completion ofreaction (TLC), the reaction mixture was poured in in cold water and theproduct was extracted in ethyl acetate (2×25 mL). The combined organicextracts were washed with water, followed by brine, dried over anhydroussodium sulfate and the product was isolated by distillation underreduced pressure. The product usually was an oily compound, which was assuch used for the next step.

The crude residue was purified by silica gel column chromatography using30% methanol in ethyl acetate as a mobile phase, to obtain the titlecompound, which was identified by IR, NMR and mass spectral analyses.

Route II:

Instead of sodium hydride (0.6 g of 50% suspension in mineral oil;0.0125 mole), either sodium hydroxide (0.03 moles) or potassiumhydroxide (0.03 moles) was taken and similar procedure was followed.

Various substituted indoles were treated with substitutedphenylsulfonylchloride as described above. These compounds wereidentified by IR, NMR and mass spectral analyses. Following is thepartial list of such compounds:

List-1:

Mass ion Description (M + H)⁺ D2 1-Benzenesulfonyl-2-phenyl-1H-indole334 D3 1-Benzenesulfonyl-2-phenyl-5-methoxy-1H-indole 364 D41-Benzenesulfonyl-2-phenyl-5-methyl-1H-indole 348 D51-Benzenesulfonyl-5-bromo-2-phenyl-1H-indole 412/414 D61-Benzenesulfonyl-5-chloro-2-phenyl-1H-indole 368/370 D71-Benzenesulfonyl-5-fluoro-2-phenyl-1H-indole 352 D81-(2′-Bromobenzenesulfonyl)-2-phenyl-1H-indole 412/414 D91-(4′-Methylbenzenesulfonyl)-5-fluoro-2-phenyl-1H- 366 indole D101-(4′-Methylbenzenesulfonyl)-5-chloro-2-phenyl-1H- 382/384 indole D111-(2′-Bromo-4′-methylbenzenesulfonyl)-2-Phenyl-1H- 426/428 indole D121-(2′-Bromo-4′-isopropylbenzenesulfonyl)-2-phenyl- 454/456 1H-indole D131-(4′-Fluorobenzenesulfonyl)-5-chloro-2-phenyl-1H-  386/3838 indole D141-Benzenesulfonyl-2-methyl-1H-indole 272 D151-Benzenesulfonyl-2-methyl-5-methoxy-1H-indole 302 D161-Benzenesulfonyl-2,5-dimethyl-1H-indole 286 D171-Benzenesulfonyl-5-bromo-2-methyl-1H-indole 350/352 D181-Benzenesulfonyl-5-chloro-2-methyl-1H-indole 306/308 D191-Benzenesulfonyl-5-fluoro-2-methyl-1H-indole 290 D201-(2′-Bromobenzenesulfonyl)-2-methyl-1H-indole 350/352 D211-(4′-Methylbenzenesulfonyl)-5-fluoro-2-methyl-1H- 304 indole D221-(4′-Methylbenzenesulfonyl)-5-chloro-2-methyl-1H- 320/322 indole D231-(2′-Bromo-4′-methylbenzenesulfonyl)-2-methyl-1H- 364/366 indole D241-(2′-Bromo-4′-isopropylbenzenesulfonyl)-2-methyl- 392/394 1H-indole D251-(4′-Fluorobenzenesulfonyl)-5-chloro-2-methyl-1H- 324 indoleDescription 26: 1-Benzenesulfonyl-2-phenyl-1H-indol-3-ol (D 26)Route 1:

1-Benzenesulfonyl-2-phenyl-1H-indole (D1) (0.01 mole) was dissolved inglacial acetic acid (15 mL) and was transferred to three-necked flask.To this mixture monoperphpthalate (0.02 moles of 50% suspension)solution in ether was added and 3 stirred at 25° C. for 3 hours. Afterthe completion of reaction, the volatile substances were removed underreduced pressure. The residue was added ethyl acetate:water (1:1)mixture, followed by sodium bicarbonate. The organic layer was separatedand the aqueous layer was extracted with ethyl acetate (3×20 mL). Thecombined organic extracts were washed with brine and the ethyl acetatewas distilled off to obtain the crude intermediate. This intermediatewas taken as such to the next step without purification.

Route 2:

Alternatively 1-Benzenesulfonyl-1H-indol-3-ol derivatives can also beobtained as reported in the Heterocycles, Vol. 30, No. 1, 1990, byreacting corresponding benzenesulfonylindoles with magnesiummonoperphthalate.)

Various other derivatives of general formula (II) were prepared asdescribed above. These compounds were identified by IR, NMR and massspectral analyses. Following is the partial list of such compounds.

List-2:

Mass ion Description (M + H)⁺ D261-Benzenesulfonyl-2-phenyl-1H-indol-3-ol 350 D271-Benzenesulfonyl-2-phenyl-5-methoxy-1H-indol-3-ol 380 D281-Benzenesulfonyl-2-phenyl-5-methyl-1H-indol-3-ol 364 D291-Benzenesulfonyl-5-bromo-2-phenyl-1H-indol-3-ol 428/430 D301-Benzenesulfonyl-5-chloro-2-phenyl-1H-indol-3-ol 384/386 D311-Benzenesulfonyl-5-fluoro-2-phenyl-1H-indol-3-ol 368 D321-(2′-Bromobenzenesulfonyl)-2-phenyl-1H-indol-3-ol 428/430 D331-(4′-Methylbenzenesulfonyl)-5-fluoro-2-phenyl-1H- 382 indol-3-ol D341-(4′-Methylbenzenesulfonyl)-5-chloro-2-phenyl-1H- 398/400 indol-3-olD35 1-(2′-Bromo-4′-methylbenzenesulfonyl)-2-phenyl-1H- 442/444indol-3-ol D36 1-(2′-Bromo-4′-isopropylbenzenesulfonyl)-2-phenyl-470/472 1H-indol-3-ol D371-(4′-Fluorobenzenesulfonyl)-5-chloro-2-phenyl- 402/404 1H-indol-3-olD38 1-Benzenesulfonyl-2-methyl-1H-indol-3-ol 288 D391-Benzenesulfonyl-2-methyl-5-methoxy-1H-indol-3-ol 318 D401-Benzenesulfonyl-2,5-dimethyl-1H-indol-3-ol 302 D411-Benzenesulfonyl-5-bromo-2-methyl-1H-indol-3-ol 366/368 D421-Benzenesulfonyl-5-chloro-2-methyl-1H-indol-3-ol 322/324 D431-Benzenesulfonyl-5-fluoro-2-methyl-1H-indol-3-ol 306 D441-(2′-Bromobenzenesulfonyl)-2-methyl-1H-indol-3-ol 366/368 D451-(4′-Methylbenzenesulfonyl)-5-fluoro-2-methyl- 320 1H-indol-3-ol D461-(4′-Methylbenzenesulfonyl)-5-chloro-2-methyl- 336/338 1H-indol-3-olD47 1-(2′-Bromo-4′-methylbenzenesulfonyl)-2-methyl- 380/3821H-indol-3-ol D48 1-(2′-Bromo-4′-isopropylbenzenesulfonyl)-2-methyl-408/410 1H-indol-3-ol D491-(4′-Fluorobenzenesulfonyl)-5-chloro-2-methyl-1H- 340/342 indol-3-olDescription 50: 1-(3-Hydroxyindol-1-yl)ethanone (D 50)

According to the methods given in literature following N-acetylindoxylswere prepared and listed as below. These compounds were identified byIR, NMR and mass spectral analyses.

List-3:

Mass ion Description (M + H)⁺ D50 1-(3-Hydroxyindol-1-yl)ethanone 176D51 1-(5-Bromo-3-hydroxyindol-1-yl)ethanone 254/256 D521-(5-Chloro-3-hydroxyindol-1-yl)ethanone 210/212 D531-(5-Fluoro-3-hydroxyindol-1-yl)ethanone 194 D541-(6-Chloro-3-hydroxyindol-1-yl)ethanone 210/212 D551-(3-Hydroxy-5-methoxyindol-1-yl)ethanone 206 D561-(5,7-Dibromo-3-hydroxyindol-1-yl)ethanone 332/334/ 336 D571-(6-Chloro-5-methoxy-3-hydroxyindol-1-yl)ethanone 240/242 D581-(6-Chloro-5-fluoro-3-hydroxyindol-1-yl)ethanone 228/230 D591-(6-Bromo-5-methoxy-3-hydroxyindol-1-yl)ethanone 284/286 D601-(6-Bromo-5-fluoro-3-hydroxyindol-1-yl)ethanone 272/274 D611-(4-Chloro-5-fluoro-3-hydroxyindol-1-yl)ethanone 228/230 D621-(4-Methoxy-5-fluoro-3-hydroxyindol-1-yl)ethanone 224 D631-(3-Hydroxy-2-phenyindol-1-yl)ethanone 252 D641-(5-Bromo-3-hydroxy-2-phenylindol-1-yl)ethanone 330/332 D651-(5-Chloro-3-hydroxy-2-phenylindol-1-yl)ethanone 286/288 D661-(5-Fluoro-3-hydroxy-2-phenylindol-1-yl)ethanone 270 D671-(6-Chloro-3-hydroxy-2-phenylindol-1-yl)ethanone 286/288 D681-(3-Hydroxy-5-methoxy-2-phenylindol-1-yl)ethanone 282 D691-(5,7-Dibromo-3-hydroxy-2-phenylindol-1- 408/410/ yl)ethanone 412 D701-(6-Chloro-5-methoxy-3-hydroxy-2-phenylindol-1- 316/318 yl)ethanone D711-(6-Chloro-5-fluoro-3-hydroxy-2-phenylindol-1- 304 yl)ethanone D721-(6-Bromo-5-methoxy-3-hydroxy-2-phenylindol-1- 360/362 yl)ethanone D731-(6-Bromo-5-fluoro-3-hydroxy-2-phenylindol-1- 348/350 yl)ethanone D741-(4-Chloro-5-fluoro-3-hydroxy-2-phenylindol-1- 304/306 yl)ethanone D751-(4-Methoxy-5-fluoro-3-hydroxy-2-Phenylindol-1- 300 yl)ethanone D761-(3-Hydroxy-2-methylindol-1-yl)ethanone 190 D771-(5-Bromo-3-hydroxy-2-methylindol-1-yl)ethanone 268/270 D781-(5-Chloro-3-hydroxy-2-methylindol-1-yl)ethanone 224 D791-(5-Fluoro-3-hydroxy-2-methylindol-1-yl)ethanone 208 D801-(6-Chloro-3-hydroxy-2-methylindol-1-yl)ethanone 224/226 D811-(3-Hydroxy-5-methoxy-2-methylindol-1-yl)ethanone 220 D821-(5,7-Dibromo-3-hydroxy-2-methylindol-1- 346/348/ yl)ethanone 350 D831-(6-Chloro-5-methoxy-3-hydroxy-2-methylindol-1- 254/256 yl)ethanone D841-(6-Chloro-5-fluoro-3-hydroxy-2-methylindol-1- 242/244 yl)ethanone D851-(6-Bromo-5-methoxy-3-hydroxy-2-methylindol-1- 298/300 yl)ethanone D861-(6-Bromo-5-fluoro-3-hydroxy-2-methylindol-1- 286/288 yl)ethanone D871-(4-Chloro-5-fluoro-3-hydroxy-2-methylindol-1- 242/244 yl)ethanone D881-(4-Methoxy-5-fluoro-3-hydroxy-2-methylindol-1- 238 yl)ethanoneDescription 89: [2-(1-Acetyl-1H-indol-3-yloxy)ethyl]dimethylamine (D 89)

According to the methods given in literature (U.S. Pat. No. 3,860,608)following derivatives were prepared and listed as below. These compoundswere identified by IR, NMR and mass spectral analyses. The followingprocedure also describes the method of synthesis of the same.

1-Acetyl-3-indoxyl (0.015 mole), was taken in three necked flask alongwith potassium carbonate (0.030 mole); tetrahydrofuran (ca 15 mL) andN,N-dimethylaminoethyl chloride (ca 15% solution in toluene; 0.015 mole)and the mixture was refluxed for 3 hours. Another, lot ofN,N-dimethylaminoethyl chloride (ca 15% solution in toluene; 0.015 mole)was added and the reaction mixture was refluxed for further 3 hours. Thereaction mixture was cooled to 25° C. and filtered. The filtrate waswashed with water and brine; dried over sodium sulfate; organic solventswere removed under reduced pressure and the residue was purified bycolumn chromatography, on silica gel; using hexane (100%) totriethylamine:ethyl acetate (2:98) gradual gradient as mobile phase, toobtain the compound of general formula (I) as thick oil, which wasidentified by IR, NMR and mass spectral analyses. The final desiredcompound of general formula (X) can be further purified by preparationof their acid addition salts.

List-4:

Mass ion Description (M + H)⁺ D89[2-(1-Acetyl-1H-Indol-3-yloxy)ethyl]dimethylamine 247 D90[2-(1-Acetyl-2-Phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 323 D91[2-(1-Acetyl-2-Methyl-1H-indol-3-yloxy)ethyl]dimethylamine 261 D92[2-(1-Acetyl-5-Bromo-1H-indol-3-yloxy)ethyl]dimethylamine 325/327 D93[2-(1-Acetyl-5-Bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine401/403 D94[2-(1-Acetyl-5-Bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine339/341 D95 [2-(1-Acetyl-5-Chloro-1H-indol-3-yloxy)ethyl]dimethylamine281/283 D96[2-(1-Acetyl-5-Chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine357/359 D97[2-(1-Acetyl-5-Chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine295/297 D98 [2-(1-Acetyl-6-Chloro-1H-indol-3-yloxy)ethyl]dimethylamine281/283 D99[2-(1-Acetyl-6-Chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine357/359 D100[2-(1-Acetyl-6-Chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine295/297 D101[2-(1-Acetyl-5,7-Dichloro-1H-indol-3-yloxy)ethyl]dimethylamine 315/317/319 D102[2-(1-Acetyl-5,7-Dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine391/393/ 395 D103[2-(1-Acetyl-5,7-Dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine329/331/ 333 D104[2-(1-Acetyl-5,7-Dibromo-1H-indol-3-yloxy)ethyl]dimethylamine 403/405/407 D105[2-(1-Acetyl-5,7-Dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine479/481/ 483 D106[2-(1-Acetyl-5,7-Dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine417/419/ 421 D107[2-(1-Acetyl-7-Bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine359/361 D108 [2-(1-Acetyl-7-Bromo-5-chloro-2-phenyl-1H-indol-3- 435/437yloxy)ethyl]dimethylamine D109[2-(1-Acetyl-7-Bromo-5-chloro-2-methyl-1H-indol-3- 373/375yloxy)ethyl]dimethylamine D110[2-(1-Acetyl-5-Methoxy-1H-indol-3-yloxy)ethyl]dimethylamine 277 D111[2-(1-Acetyl-5-Methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 353D112[2-(1-Acetyl-5-Methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine 291Description 113: [2-(1H-indol-3-yloxy)ethyl]dimethylamine (D 113)

According to the methods given in literature (U.S. Pat. No. 3,860,608)the above derivatives were deacetylated. These compounds were identifiedby IR, NMR and mass spectral analyses. The following procedure alsodescribes the method of synthesis of above compounds,

[2-(1-Acetyl-1H-indol-3-yloxy)ethyl]dimethylamine (0.015 mole), wastaken in three necked flask along with sodium hydroxide (0.022 mole),water (ca 15 mL) and methanol (ca 15 mL). The reaction mixture wasrefluxed for 30 minutes to 2 hours. The reaction mixture was cooled to25° C. and poured on to ice-cold water. The compound was extracted withethyl acetate (3×20 mL), the combined organic extracts were washed withwater and brine; dried over sodium sulfate; organic solvents wereremoved under reduced pressure and the residue was purified by columnchromatography, on silica gel; using hexane (100%) totriethylamine:ethyl acetate (2:98) gradual gradient as mobile phase, toobtain the compound of general formula (I) as thick oil, which wasidentified by IR, NMR and mass spectral analyses. The final desiredcompound of general formula (IV) can be further purified by preparationof their acid addition salts.

List-5:

Mass ion Description (M + H)⁺ D113[2-(1H-Indol-3-yloxy)ethyl]dimethylamine 205 D114[2-(2-Phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 281 D115[2-(2-Methyl-1H-indol-3-yloxy)ethyl]dimethylamine 219 D116[2-(5-Bromo-1H-indol-3-yloxy)ethyl]dimethylamine 283/285 D117[2-(5-Bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 359/361 D118[2-(5-Bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine 297/298 D119[2-(5-Chloro-1H-indol-3-yloxy)ethyl]dimethylamine 239/241 D120[2-(5-Chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 315/317 D121[2-(5-Chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine 253/255 D122[2-(6-Chloro-1H-indol-3-yloxy)ethyl]dimethylamine 239/241 D123[2-(6-Chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 315/317 D124[2-(6-Chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine 253/255 D125[2-(5,7-Dichloro-1H-indol-3-yloxy)ethyl]dimethylamine 273/275/ 277 D126[2-(5,7-Dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 349/351/353 D127 [2-(5,7-Dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine287/289/ 291 D128 [2-(5,7-Dibromo-1H-indol-3-yloxy)ethyl]dimethylamine361/363/ 365 D129[2-(5,7-Dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 437/439/441 D130 [2-(5,7-Dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine375/377/ 379 D131[2-(7-Bromo-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine 317/319/ 321D132 [2-(7-Bromo-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine393/395/ 397 D133[2-(7-Bromo-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine331/333/ 335 D134 [2-(5-Methoxy-1H-indol-3-yloxy)ethyl]dimethylamine 235D135 [2-(5-Methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine 311D136 [2-(5-Methoxy-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine 249

Example-1[2-(1-(4′-Bromobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Sodium hydride (60% in mineral oil, 16.5 mmoles) was stirred withdimethyl formamide (ca 8 mL) in a ice-cooled, three necked round bottomflask. A solution of [2-(1H-indol-3-yloxy)ethyl]dimethylamine (15mmole), in dimethyl formamide (ca 5 mL) was then added dropwise to thiscooled suspension of sodium hydride. After the addition was complete,the reaction mixture was allowed to attain the room temperature (25°C.). After about one hour of stirring at 25° C., a solution of4-Bromobenzenesulfonyl chloride (18 mmole) was added dropwise to thissolution. The reaction was further stirred at 25° C. for next 3-4 hours.After the completion of reaction (TLC), reaction mixture was poured onthe ice cooled water and extracted by Ethyl acetate (3×20 mL). Thecombined organic extract was washed with water and brine, dried oversodium sulphate and the volatiles were evaporated under vacuum to getthe product as a thick dark oil. The residue was purified by columnchromatography, on silica gel; using hexane (100%) totriethylamine:ethyl acetate (2:98) gradual gradient as mobile phase, toobtain the compound of general formula (I) as thick oil, which wasidentified by IR, NMR and mass spectral analyses. The final desiredcompound of general formula (I) can be further purified by preparationof their acid addition salts. Melting range (° C.): Isolated as oil;Mass (m/z): 423, 425 (M+H)⁺; IR spectra (cm⁻¹): 1150 (SO₂); ¹H-NMR(ppm): 2.40 (s, 6H); 2.83-2.88 (t, 2H, J=5.4 Hz); 4.11-4.16 (t, 2H,J=5.4 Hz); 6.87 (s, 1H); 7.19-7.38 (m, 3H); 7.50-7.67 (m, 4H); 7.95-7.99(d, 1H).

Example-2[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150 (SO₂), 2900 (C—Hstretch); Mass (m/z): 437, 439 (M+H)⁺; ¹H-NMR (ppm): 2.33 (s, 3H); 2.38(s, 6H); 2.80-2.85 (t, 2H, J=5.4 Hz); 4.12-4.17 (t, 2H, J=5.4 Hz); 7.13(s, 1H); 7.20-7.26 (m, 3H); 7.47 (d, 1H); 7.57-7.58 (m, 1H); 7.77-7.81(m, 2H)

Example-3[2-(1-(2*-Bromobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150 (SO₂), 2900 (C—Hstretch); Mass (m/z): 423, 425 (M+H)⁺; 1H-NMR (ppm): 2.36 (s, 6H);2.77-2.83 (t, 2H, J=5.4 Hz); 4.11-4.16 (t, 2H, J=5.4 Hz); 7.13 (s, 1H);7.18-7.41 (m, 4H); 7.59-7.84 (m, 4H)

Example-4[2-(1-(4′-Fluorobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150 (SO₂), 2900 (C—Hstretch); Mass (m/z): 363 (M+H)⁺; ¹H-NMR (ppm): 2.38 (s, 6H); 2.80-2.86(t, 2H, J=5.4 Hz); 4.09-4.15 (t, 2H, J=5.4 Hz); 6.88 (s, 1H); 7.01-7.10(m, 2H); 7.22-738 (m, 2H); 7.51-7.55 (dd, 1H); 7.78-7.85 (m, 2H);7.96-8.00 (dd, 1H)

Example-5[2-(1-(4′-Chlorobenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150 (SO₂), 2900 (C—Hstretch); Mass (m/z): 379.1 (M+H)⁺; ¹H-NMR (ppm): 2.36 (s, 6H);2.79-2.82 (t, 2H, J=5.4 Hz); 4.07-4.13 (t, 2H, J=5.4 Hz); 6.87 (s, 1H);7.18-7.38 (m, 4H); 7.52-7.56 (dd, 1H); 7.51-7.55 (dd, 1H); 7.69-7.76 (d,2H); 7.95-7.99 (d, 1H)

Example-6[2-(1-(4′-Methylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150 (SO₂), 2900 (C—Hstretch); Mass (m/z): 359.3 (M+H)⁺

Example-7[2-(1-(4′-Isopropylbenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1155; Mass (m/z): 387(M+H)⁺;

Example-8[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 453,455 (M+H)⁺;

Example-9 [2-(1-(Benzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1152; Mass (m/z): 345(M+H)⁺;

Example-10[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 405(M+H)⁺;

Example-11[2-(1-Benzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z):421.5 (M+H)⁺;

Example-12[2-(1-(4′-Fluorobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z):439.4 (M+H)⁺;

Example-13[2-(1-4′-Bromobenzenesulfonyl)-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 499,501 (M+H)⁺;

Example-14[2-(1-(4′-Isopropylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1155; Mass (m/z):463.4 (M+H)⁺;

Example-15[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1153; Mass (m/z):481.3 (M+H)⁺;

Example-16[2-(1-(4′-Methylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹); 1154; Mass (m/z):435.3 (M+H)⁺;

Example-17[2-(1-(4′-Chlorobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 455,457 (M+H)⁺;

Example-18[2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1152; Mass (m/z): 513,515 (M+H)⁺;

Example-19[2-(1-(2′-Bromo-4′-Methoxybenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 529,531 (M+H)⁺;

Example-20[2-(1-(2′-Bromobenzenesulfonyl)-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z): 499,501 (M+H)⁺;

Example-21[2-(1-Benzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1155; Mass (m/z):359.3 (M+H)⁺;

Example-22[2-(1-(4′-fluorobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z):377.3 (M+H)⁺;

Example-23[2-(1-(4′-Bromobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z); 437,439 (M+H)⁺;

Example-24[2-(1-(4′-Isopropylbenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1152; Mass (m/z):401.4 (M+H)⁺;

Example-25[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z):419.5 (M+H)⁺;

Example-26[2-(1-(2′-Bromobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1155; Mass (m/z): 437,439 (M+H)⁺;

Example-27[2-(1-(2′-Bromo-4′-Methylbenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 451,453 (M+H)⁺;

Example-28[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 467,469 (M+H)⁺;

Example-29[2-(1-(4′-Chlorobenzenesulfonyl)-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z): 394,396 (M+H)⁺;

Example-30[2-(1-(4′-Isopropylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): 105-107; IR spectra (cm⁻¹): 1174.57 (SO₂), 2962, 2967 (C—HStretching); Mass (m/z): 465, 467.3 (M+H)⁺; ¹H-NMR (ppm): 1.17-1.2 (d,6H,); 2.2 (s, 6H); 2.78 (t, 2H, J=5.4 Hz); 2.81 (septet, 1H); 4.06-4.11(t, 2H, J=5.4 Hz); 6.918 (s, 1H); 7.22-7.26 (d, 2H); 7.39-7.44 (dd, 1H);7δ-7.9 (m, 4H);

Example-31[2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1178.49 (SO₂); Mass(m/z): 501, 503, 505 (M+H)⁺; ¹H-NMR (ppm): 2.3 (s, 6H); 2.74 (t, 2H);4.02-4.08 (t, 2H); 7.04 (s, 1H); 7.29-7.35 (m, 3H); 7.52-7.81 (m, 4H)

Example-32[2-(1-Benzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; 224-226 (HCl salt); IR spectra (cm⁻¹):1176.32 (SO₂); Mass (m/z): 423, 425 (M+H)⁺; ¹H-NMR (ppm): D3.02 (s, 6H);3.65-3.67 (t, 2H, J=5.4 Hz); 4.43-4.47 (t, 2H, J=5.4 Hz); 7.37 (s, 1H);7.48-7.64, (m, 4H); 7.78-7.79 (d, 1H); 7.94-7.99 (m, 3H)

Example-33[2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): 74-75; IR spectra (cm⁻¹): 1180.57 (SO₂); Mass (m/z): 441,443 (M+H)⁺; ¹H-NMR (ppm): □2.35 (s, 6H); 2.73-2.79 (t, 2H, J=5.4 Hz);4.04-4.1 (t, 2H, J=5.4 Hz); 6.87 (s, 1H); 7.08-7.12 (d, 2H); 7.40-7.45(dd, 1H); 7.68-7.83 (m, 4H).

Example-34[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1150; Mass (m/z): 531,533, 535 (M+H)⁺;

Example-35[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z): 515,517 (M+H)⁺;

Example-36[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z): 483,485 (M+H)⁺;

Example-37[2-(1-(4′-Bromobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1154; Mass (m/z): 501,503, 505 (M+H)⁺;

Example-38[2-(1-(4′-Chlorobenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1155; Mass (m/z): 457,459, 461 (M+H)⁺;

Example-39[2-(1-(4′-Methylbenzenesulfonyl)-5-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 437, 439 (M+H)⁺; ¹H-NMR (ppm): □2.35 (s, 3H); 3.01 (s, 6H);3.65-3.70 (t, 2H, J=5.4 Hz); 4.42-4.47 (t, 2H, J=5.4 Hz); 7.33-7.34 (d,2H); 7.47-7.81 (d, 5H); 7.91-7.96 (d, 1H).

Example-40[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-5-bromo-2-Methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 329, 531, 533 (M+H)⁺;

Example-41[2-(1-(2′-Bromobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 515, 517, 519 (M+H)⁺;

Example-42[2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 455, 457 (M+H)⁺;

Example-43[2-(1-(4′-Fluorobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 517, 519 (M+H)⁺;

Example-44[2-(1-(4′-Chlorobenzenesulfonyl)-5-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 533, 535, 537 (M+H)⁺;

Example-45[2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1160 (SO₂); Mass(m/z): 519, 521, 523 (M+H)⁺;

Example-46[2-(1-(4′-Chlorobenzenesulfonyl)-5,7-dibromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 535, 537, 539 (M+H)⁺;

Example-47[2-(1-4′-Fluorobenzenesulfonyl)-5,7-dibromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated, as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 595, 597, 599 (M+H)⁺;

Example-48[2-(1-(4′-Methylbenzenesulfonyl)-5,7-dibromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1166 (SO₂); Mass(m/z): 529, 531, 533 (M+H)⁺;

Example-49[2-(1-(4′-Fluorobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1165; Mass (m/z): 397,399 (M+H)⁺; ¹H-NMR (δ□□ ppm): 2.37 (s, 6H); 2.77-2.83 (t, 2H, J=5.4 Hz);4.06-4.12 (t, 2H, J=5.4 Hz); 6.86 (s, 1H); 7.06-7.26 (m, 3H); 7.44-7.48(d, 1H); 7.79-7.86 (m, 2H); 8.00-8.01 (d, 1H).

Example-50[2-(1-(2′-Bromobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1160; Mass (m/z): 457,459, 461 (M+H)⁺;

Example-51[2-(1-(4′-Methylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1173.4 (SO₂); 812, 786(C—Cl) Mass (m/z): 393, 395 (M+H)⁺; ¹H-NMR (δ□□ ppm): 2.35 (s, 9H, CH₃and NMe₂); 2.74-2.8 (t, 2H, J=5.4 Hz); 4.05-4.10 (t, 2H, J=5.4 Hz); 6.88(s, 1H); 7.15-7.26 (m, 3H); 7.42-7.46 (d, 1H); 7.66-7.71 (d, 2H);8.01-8.02 (d, 1H).

Example-52[2-(1-Benzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 379, 381 (M+H)⁺; 1H-NMR (δ□□ ppm): 2.34 (s, 6H);2.72-2.78 (t, 2H, J=5.4 Hz); 4.01-4.10 (t, 2H, J=5.4 Hz); 6.89 (s, 1H);7.16-7.26 (dd, 1H); 7.38-7.57 (m, 4H); 7.78-7.82 (m, 2H); 8.02-8.03 (d,1H).

Example-53[2-(1-(4′-Isopropylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 421, 423 (M+H)⁺;

Example-54[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 487, 489, 491 (M+H)⁺.

Example-55[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 471, 473, 475 (M+H)⁺.

Example-56[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 439, 441 (M+H)⁺.

Example-57[2-(1-(4′-Bromobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared.

Melting range (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂);815, 787 (C—Cl) Mass (m/z): 457, 459, 461 (M+H)⁺.

Example-58[2-(1-(4′-Chlorobenzenesulfonyl)-6-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 413, 415, 417 (M+H)⁺;

Example-59[2-(1-(4′Fluorobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1165; Mass (m/z): 397,399 (M+H)⁺; ¹H-NMR (δ□□ ppm): 2.37 (s, 6H); 2.77-2.83 (t, 2H, J=5.4 Hz);4.06-4.12 (t, 2H, J=5.4 Hz); 6.86 (s, 1H); 7.06-7.26 (m, 3H); 7.44-7.48(d, 1H); 7.79-7.86 (m, 2H); 8.00-8.01 (d, 1H).

Example-60[2-(1-(2′Bromobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1167; Mass (m/z): 457,459, 461 (M+H)⁺;

Example-61[2-(1-(4′-Methylbenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1173.4 (SO₂); 812, 786(C—Cl); Mass (m/z): 393, 395 (M+H)⁺; ¹H-NMR (δ□□ ppm): 2.35 (s, 9H, CH₃and NMe₂); 2.74-2.8 (t, 2H, J=5.4 Hz); 4.05-4.10 (t, 2H, J= 5.4 Hz);6.88 (s, 1H); 7.15-7.26 (m, 3H); 7.42-7.46 (d, 1H); 7.66-7.71 (d, 2H);8.01-8.02 (d, 1H).

Example-62[2-(1-(Benzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl) Mass (m/z): 379, 381 (M+H)⁺; ¹H-NMR (δ□□ ppm): 2.34 (s, 6H);2.72-2.78 (t, 2H, J=5.4 Hz); 4.01-4.10 (t, 2H, J=5.4 Hz); 6.89 (s, 1H);7.16-7.26 (dd, 1H); 7.38-7.57 (m, 4H); 7.78-7.82 (m, 2H); 8.02-8.03 (d,1H).

Example-63[2-(1-(4′-Isopropylbenzenesulfonyl)-5-Chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 421, 423 (M+H)⁺.

Example-64[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 487, 489, 491 (M+H)⁺.

Example-65[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 471, 473, 475 (M+H)⁺.

Example-66[2-(1-(3′,4′-Dimethoxybenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 439 (M+H)⁺.

Example-67[2-(1-(4′-Bromobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 457, 459, 461 (M+H)⁺.

Example-68[2-(1-(4′-Chlorobenzenesulfonyl)-5-chloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 413, 415, 417 (M+H)⁺.

Example-69[2-(1-Benzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 455, 457 (M+H)⁺.

Example-70[2-(1-(2′-Bromo-4′-methylbenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 547, 549, 551 (M+H)⁺.

Example-71[2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 473, 475 (M+H)⁺.

Example-72[2-(1-(Benzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 393, 395 (M+H)⁺.

Example-73[2-(1-(4-Fluorobenzenesulfonyl)-5-chloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 411, 413 (M+H)⁺.

Example-74[2-(1-(4′-Fluorobenzenesulfonyl)-5,7-dichloro-1H-Indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 431, 433, 435 (M+H)⁺.

Example-75[2-(1-(2′-Bromobenzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 491, 493, 495 (M+H)⁺.

Example-76[2-(1-(Benzenesulfonyl)-5,7-dichloro-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 413, 415, 417 (M+H)⁺.

Example-77[2-(1-(Benzenesulfonyl)-5,7-dichloro-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 427, 429, 431 (M+H)⁺.

Example-78[2-(1-Benzenesulfonyl)-5,7-dichloro-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 489, 491, 493 (M+H)⁺.

Example-79[2-(1-(4′Methyl-Benzenesulfonyl)-5,7-Dichloro,2-Phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 503, 505, 507 (M+H)⁺.

Example-80[2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-7-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 475, 477, 479 (M+H)⁺.

Example-81[2-(1-(4′-Chlorobenzenesulfonyl)-5-chloro-7-bromo-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 491, 493, 495.

Example-82[2-(1-Benzenesulfonyl)-5-Chloro-7-bromo-2-methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 471, 473, 475 (M+H)⁺.

Example-83[2-(1-(2′-Bromo-4′-methoxybenzenesulfonyl)-5-Chloro-7-Bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 641, 643, 645 (M+H)⁺.

Example-84[2-(1-(4′-Fluorobenzenesulfonyl)-5-chloro-7-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 551, 553, 555 (M+H)⁺.

Example-85[2-(1-(4′-Bromobenzenesulfonyl)-5-chloro-7-bromo-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); 815,787 (C—Cl); Mass (m/z): 611, 613, 615 (M+H)⁺.

Example-86[2-(1-Benzenesulfonyl)-5-methoxy-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 375.4 (M+H)⁺.

Example-87[2-(1-(4′-Bromobenzenesulfonyl)-5-Methoxy-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂) Mass(m/z): 453, 455 (M+H)⁺.

Example-88[2-(1-(4′-Fluorobenzenesulfonyl)-5-Methoxy-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 393.4 (M+H)⁺.

Example-89[2-(1-(4′-Chlorobenzenesulfonyl)-5-Methoxy-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 409, 411 (M+H)⁺.

Example-90[2-(1-Benzenesulfonyl)-5-Methoxy-2-Methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 389.4 (M+H)⁺.

Example-91[2-(1-(4′-Fluorobenzenesulfonyl)-5-Methoxy-2-Methyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 407.4 (M+H)⁺.

Example-92[2-(1-(4′-Fluorobenzenesulfonyl)-5-methoxy-2-phenyl-1H-indol-3-yloxy)ethyl]dimethylamine

Using essentially the general procedure described in example 1 and somenon-critical variations, the above derivative was prepared. Meltingrange (° C.): Isolated as oil; IR spectra (cm⁻¹): 1176.21 (SO₂); Mass(m/z): 469.5 (M+H)⁺.

1. A method of treatment of a disorder or medical condition selectedfrom obesity, Alzheimer's, cognition and schizophrenia, which comprisesadministering to a patient a therapeutically effective amount of acompound of general formula (I):

its stereoisomers, its radioisotopes, its geometric forms, its N-oxide,its pharmaceutically acceptable salts, wherein R₁, R₂, R₃, R₄, R₅, R₆,R₇, R₈, R₉, may be same or different, and represent hydrogen, halogen,hydroxyl, substituted or unsubstituted groups selected from linear orbranched (C₁-C₃) alkyl and (C₁-C₃) alkoxy, R₁₀ represents hydrogen,halogen, hydroxyl, substituted or unsubstituted groups selected fromlinear or branched (C₁-C₃) alkyl and aryl; R₁₁, R₁₂, R₁₃ and R₁₄ may besame or different, and represent hydrogen and substituted orunsubstituted groups selected from linear or branched (C1-C3) alkyl; “n”is an integer value representing 2; and “m” is an integer ranging from 0to 2 and preferably m is 1 or
 2. 2. A process for the preparation of acompound of general formula (I)

its stereoisomers, its radioisotopes, its geometric forms, its N-oxide,its pharmaceutically acceptable salts, wherein R₁, R₂, R₃, R₄, R₅, R₆,R₇, R₈, R₉, may be same or different, and represent hydrogen, halogen,hydroxyl, substituted or unsubstituted groups selected from linear orbranched (C₁-C₃) alkyl and (C₁-C₃) alkoxy, R₁₀ represents hydrogen,halogen, hydroxyl, substituted or unsubstituted groups selected fromlinear or branched (C₁-C₃) alkyl and aryl; R₁₁, R₁₂, R₁₃ and R₁₄ may besame or different, and represent hydrogen and substituted orunsubstituted groups selected from linear or branched (C1-C3) alkyl; “n”is an integer value representing 2; and “m” is an integer ranging from 0to 2 and preferably m is 1 or 2; the process comprising: a) reacting acompound of formula (II),

where R represents either a suitable N-protecting groups or a group suchas

with a compound of formula (III) or its acid addition salt,

to obtain compound of general formula (I), wherein Lg is a leavinggroup.